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TDMS Study 05002-05 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                               GAMMA-BUTYROLACTONE                                  DATE: 09/02/94       
EXPERIMENT: 05002 TEST: 05                                                                                     TIME: 18:09:28       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1CP9565101          ROUTE: GAVAGE                                                                      NTP C#: 55878        
PATHOLOGIST: R. THOMPSON                     S. EUSTIS                                                         CAS: 96-48-0         
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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: Southern Research Inst                               GAMMA-BUTYROLACTONE                                  DATE: 09/02/94      
EXPERIMENT: 05002 TEST: 05                                                                                     TIME: 18:09:28      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: NO1CP9565101          ROUTE: GAVAGE                                                                      NTP C#: 55878       
PATHOLOGIST: R. THOMPSON                     S. EUSTIS                                                         CAS: 96-48-0        
 
 
 
 
 
                                                    RATS(FISCHER344)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Gland
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                               GAMMA-BUTYROLACTONE                                  DATE: 09/02/94       
EXPERIMENT: 05002 TEST: 05                                                                                     TIME: 18:09:28       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1CP9565101          ROUTE: GAVAGE                                                                      NTP C#: 55878        
PATHOLOGIST: R. THOMPSON                     S. EUSTIS                                                         CAS: 96-48-0         
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                      IN THE ANALYSIS OF THE STUDY OF GAMMA-BUTYROLACTONE
 
              ====================================================================================================
 
                                                           MALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Adrenal Medulla               Pheochromocytoma Benign
                                                           Pheochromocytoma Malignant
                                                           Pheochromocytoma: Benign, Complex, Malignant, NOS
                             Clitoral/Preputial Gland      Adenoma
                                                           Carcinoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                             Skin                          Keratoacanthoma
                                                           Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,
                                                            Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma
                             Skin: Subcutaneous Tissue     Fibrosarcoma
                                                           Neurofibrosarcoma, Fibrosarcoma, or Sarcoma
                             Testes                        Adenoma
                             Thyroid Gland: C-Cell         Carcinoma or Adenoma
                             All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear,
                                                            or Undifferentiated
                                                           Mesothelioma Benign, Malignant, NOS
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                               GAMMA-BUTYROLACTONE                                  DATE: 09/02/94       
EXPERIMENT: 05002 TEST: 05                                                                                     TIME: 18:09:28       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1CP9565101          ROUTE: GAVAGE                                                                      NTP C#: 55878        
PATHOLOGIST: R. THOMPSON                     S. EUSTIS                                                         CAS: 96-48-0         
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                      IN THE ANALYSIS OF THE STUDY OF GAMMA-BUTYROLACTONE
 
              ====================================================================================================
 
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Adrenal Medulla               Pheochromocytoma Malignant
                             Clitoral/Preputial Gland      Adenoma
                                                           Carcinoma or Adenoma
                             Mammary Gland                 Carcinoma
                                                           Fibroadenoma
                                                           Fibroma, Fibroadenoma or Adenoma
                                                           Fibroma, Fibroadenoma, Carcinoma, or Adenoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             All Organs                    Hemangiosarcoma
                                                           Hemangiosarcoma or Hemangioma
 
              ====================================================================================================
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE   1
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/48 (2%)       0/24 (0%)       1/49 (2%)      |     1/50 (2%)       0/25 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |      4.2%            0.0%            3.2%          |      3.6%            0.0%            6.2%          |
|TERMINAL (d)           |     1/24 (4%)       0/1 (0%)        1/31 (3%)      |     1/28 (4%)       0/2 (0%)        1/28 (4%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         ---             729 (T)       |      730 (T)         ---             653           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.573N        P=0.991N        P=0.704N       |     P=0.371         P=0.959N        P=0.491        |
|INCIDENTAL TUMOR       |     P=0.573N        P=0.991N        P=0.704N       |     P=0.349         P=0.959N        P=0.458        |
|LOGISTIC REGRESSION    |     P=0.573N        P=0.991N        P=0.704N       |     P=0.358         P=0.961N        P=0.480        |
|COCHRAN-ARMITAGE       |     P=0.651N                                       |     P=0.372                                        |
|FISHER EXACT           |                     P=0.667N        P=0.747N       |                     P=0.667N        P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    15/48 (31%)     10/23 (43%)     14/49 (29%)     |     1/50 (2%)       0/25 (0%)       4/49 (8%)      |
|ADJUSTED (b)           |     59.8%          100.0%           36.9%          |      3.3%            0.0%           13.7%          |
|TERMINAL (d)           |    14/24 (58%)      1/1 (100%)      9/31 (29%)     |     0/28 (0%)       0/2 (0%)        3/28 (11%)     |
|FIRST INCIDENCE (DAYS) |      681             489             365           |      716             ---             726           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.181N        P=0.013 *       P=0.216N       |     P=0.111         P=0.514N        P=0.185        |
|INCIDENTAL TUMOR       |     P=0.244N        P=0.002 **      P=0.213N       |     P=0.086         P=0.485N        P=0.139        |
|LOGISTIC REGRESSION    |     P=0.356N        P=0.025 *       P=0.218N       |     P=0.109         P=0.749N        P=0.090        |
|COCHRAN-ARMITAGE       |     P=0.428N                                       |     P=0.097                                        |
|FISHER EXACT           |                     P=0.227         P=0.473N       |                     P=0.667N        P=0.175        |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE   2
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Malignant                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/48 (0%)       1/23 (4%)       5/49 (10%)     |     0/50 (0%)       1/25 (4%)       0/49 (0%)      |
|ADJUSTED (b)           |      0.0%            2.4%           15.4%          |      0.0%           50.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       0/1 (0%)        4/31 (13%)     |     0/28 (0%)       1/2 (50%)       0/28 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             590             704           |      ---             730 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.042 *       P=0.515         P=0.061        |     P=0.695         P=0.041 *         (e)          |
|INCIDENTAL TUMOR       |     P=0.030 *       P=0.450         P=0.054        |     P=0.695         P=0.041 *         (e)          |
|LOGISTIC REGRESSION    |     P=0.030 *       P=0.427         P=0.056        |     P=0.695         P=0.039 *         (e)          |
|COCHRAN-ARMITAGE       |     P=0.019 *                                      |     P=0.710                                        |
|FISHER EXACT           |                     P=0.324         P=0.030 *      |                     P=0.333           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    15/48 (31%)     10/23 (43%)     19/49 (39%)     |     1/50 (2%)       1/25 (4%)       4/49 (8%)      |
|ADJUSTED (b)           |     59.8%          100.0%           49.9%          |      3.3%           50.0%           13.7%          |
|TERMINAL (d)           |    14/24 (58%)      1/1 (100%)     13/31 (42%)     |     0/28 (0%)       1/2 (50%)       3/28 (11%)     |
|FIRST INCIDENCE (DAYS) |      681             489             365           |      716             730 (T)         726           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.498N        P=0.013 *       P=0.578N       |     P=0.134         P=0.535         P=0.185        |
|INCIDENTAL TUMOR       |     P=0.470         P=0.002 **      P=0.579        |     P=0.108         P=0.561         P=0.139        |
|LOGISTIC REGRESSION    |     P=0.342         P=0.025 *       P=0.581        |     P=0.130         P=0.394         P=0.090        |
|COCHRAN-ARMITAGE       |     P=0.255                                        |     P=0.116                                        |
|FISHER EXACT           |                     P=0.227         P=0.287        |                     P=0.559         P=0.175        |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE   3
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/48 (13%)      1/24 (4%)       2/50 (4%)      |     6/48 (13%)      5/22 (23%)      5/46 (11%)     |
|ADJUSTED (b)           |     18.3%           50.0%            6.3%          |     20.3%           76.4%           17.7%          |
|TERMINAL (d)           |     1/24 (4%)       1/2 (50%)       2/32 (6%)      |     5/28 (18%)      3/4 (75%)       4/27 (15%)     |
|FIRST INCIDENCE (DAYS) |      481             729 (T)         729 (T)       |      683             652             726           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.049N*       P=0.144N        P=0.081N       |     P=0.471N        P=0.049 *       P=0.525N       |
|INCIDENTAL TUMOR       |     P=0.076N        P=0.169N        P=0.148N       |     P=0.522N        P=0.048 *       P=0.573N       |
|LOGISTIC REGRESSION    |     P=0.071N        P=0.276N        P=0.125N       |     P=0.491N        P=0.113         P=0.537N       |
|COCHRAN-ARMITAGE       |     P=0.080N                                       |     P=0.473N                                       |
|FISHER EXACT           |                     P=0.250N        P=0.121N       |                     P=0.227         P=0.530N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/48 (2%)       4/24 (17%)      3/50 (6%)      |     0/48 (0%)       0/22 (0%)       1/46 (2%)      |
|ADJUSTED (b)           |      4.2%           54.1%            6.7%          |      0.0%            0.0%            2.9%          |
|TERMINAL (d)           |     1/24 (4%)       1/2 (50%)       0/32 (0%)      |     0/28 (0%)       0/4 (0%)        0/27 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         593             550           |      ---             ---             670           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.359         P=0.029 *       P=0.379        |     P=0.264           (e)           P=0.500        |
|INCIDENTAL TUMOR       |     P=0.204         P=0.016 *       P=0.236        |     P=0.210           (e)           P=0.419        |
|LOGISTIC REGRESSION    |     P=0.269         P=0.015 *       P=0.280        |     P=0.278           (e)           P=0.488        |
|COCHRAN-ARMITAGE       |     P=0.290                                        |     P=0.282                                        |
|FISHER EXACT           |                     P=0.039 *       P=0.324        |                       (e)           P=0.489        |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE   4
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     7/48 (15%)      5/24 (21%)      5/50 (10%)     |     6/48 (13%)      5/22 (23%)      6/46 (13%)     |
|ADJUSTED (b)           |     21.9%          100.0%           12.6%          |     20.3%           76.4%           20.1%          |
|TERMINAL (d)           |     2/24 (8%)       2/2 (100%)      2/32 (6%)      |     5/28 (18%)      3/4 (75%)       4/27 (15%)     |
|FIRST INCIDENCE (DAYS) |      481             593             550           |      683             652             670           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.199N        P=0.491         P=0.251N       |     P=0.529         P=0.049 *       P=0.598        |
|INCIDENTAL TUMOR       |     P=0.351N        P=0.393         P=0.447N       |     P=0.464         P=0.048 *       P=0.529        |
|LOGISTIC REGRESSION    |     P=0.300N        P=0.266         P=0.388N       |     P=0.498         P=0.113         P=0.573        |
|COCHRAN-ARMITAGE       |     P=0.301N                                       |     P=0.524                                        |
|FISHER EXACT           |                     P=0.361         P=0.351N       |                     P=0.227         P=0.590        |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/49 (6%)       0/22 (0%)       3/50 (6%)      |     1/49 (2%)       0/24 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |     10.7%            0.0%            7.8%          |      3.6%            0.0%            0.0%          |
|TERMINAL (d)           |     2/24 (8%)       0/0             1/32 (3%)      |     1/28 (4%)       0/1 (0%)        0/28 (0%)      |
|FIRST INCIDENCE (DAYS) |      596             ---             609           |      730 (T)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.482N        P=0.495N        P=0.550N       |     P=0.307N        P=0.995N        P=0.500N       |
|INCIDENTAL TUMOR       |     P=0.575N        P=0.523N        P=0.651        |     P=0.307N        P=0.995N        P=0.500N       |
|LOGISTIC REGRESSION    |     P=0.561N        P=0.369N        P=0.653N       |     P=0.307N        P=0.995N        P=0.500N       |
|COCHRAN-ARMITAGE       |     P=0.584N                                       |     P=0.285N                                       |
|FISHER EXACT           |                     P=0.322N        P=0.651N       |                     P=0.671N        P=0.495N       |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE   5
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/49 (4%)       1/22 (5%)       0/50 (0%)      |     0/49 (0%)       0/24 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      5.7%            0.0%            0.0%          |      0.0%            0.0%            3.6%          |
|TERMINAL (d)           |     0/24 (0%)       0/0             0/32 (0%)      |     0/28 (0%)       0/1 (0%)        1/28 (4%)      |
|FIRST INCIDENCE (DAYS) |      641             712             ---           |      ---             ---             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.111N        P=0.472N        P=0.198N       |     P=0.307           (e)           P=0.500        |
|INCIDENTAL TUMOR       |     P=0.158N        P=0.514N        P=0.290N       |     P=0.307           (e)           P=0.500        |
|LOGISTIC REGRESSION    |     P=0.157N        P=0.672         P=0.250N       |     P=0.307           (e)           P=0.500        |
|COCHRAN-ARMITAGE       |     P=0.162N                                       |     P=0.291                                        |
|FISHER EXACT           |                     P=0.678         P=0.242N       |                       (e)           P=0.505        |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     5/49 (10%)      1/22 (5%)       3/50 (6%)      |     1/49 (2%)       0/24 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |     15.8%            0.0%            7.8%          |      3.6%            0.0%            3.6%          |
|TERMINAL (d)           |     2/24 (8%)       0/0             1/32 (3%)      |     1/28 (4%)       0/1 (0%)        1/28 (4%)      |
|FIRST INCIDENCE (DAYS) |      596             712             609           |      730 (T)         ---             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.186N        P=0.285N        P=0.249N       |     P=0.641N        P=0.995N        P=0.762        |
|INCIDENTAL TUMOR       |     P=0.278N        P=0.324N        P=0.399N       |     P=0.641N        P=0.995N        P=0.762        |
|LOGISTIC REGRESSION    |     P=0.255N        P=0.476N        P=0.463N       |     P=0.641N        P=0.995N        P=0.762        |
|COCHRAN-ARMITAGE       |     P=0.274N                                       |     P=0.650N                                       |
|FISHER EXACT           |                     P=0.391N        P=0.346N       |                     P=0.671N        P=0.747N       |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE   6
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/29 (3%)       3/50 (6%)      |     0/50 (0%)       1/30 (3%)       2/50 (4%)      |
|ADJUSTED (b)           |      5.7%           16.7%            9.4%          |      0.0%            2.4%            7.1%          |
|TERMINAL (d)           |     0/24 (0%)       1/6 (17%)       3/32 (9%)      |     0/28 (0%)       0/7 (0%)        2/28 (7%)      |
|FIRST INCIDENCE (DAYS) |      641             729 (T)         729 (T)       |      ---             652             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.528         P=0.637N        P=0.612        |     P=0.162         P=0.505         P=0.238        |
|INCIDENTAL TUMOR       |     P=0.470         P=0.669N        P=0.526        |     P=0.147         P=0.515         P=0.238        |
|LOGISTIC REGRESSION    |     P=0.475         P=0.726N        P=0.541        |     P=0.152         P=0.401         P=0.238        |
|COCHRAN-ARMITAGE       |     P=0.406                                        |     P=0.159                                        |
|FISHER EXACT           |                     P=0.697N        P=0.500        |                     P=0.375         P=0.247        |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/29 (3%)       4/50 (8%)      |     1/50 (2%)       1/30 (3%)       2/50 (4%)      |
|ADJUSTED (b)           |      5.7%           16.7%           12.5%          |      3.6%            2.4%            7.1%          |
|TERMINAL (d)           |     0/24 (0%)       1/6 (17%)       4/32 (13%)     |     1/28 (4%)       0/7 (0%)        2/28 (7%)      |
|FIRST INCIDENCE (DAYS) |      641             729 (T)         729 (T)       |      730 (T)         652             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.380         P=0.637N        P=0.461        |     P=0.385         P=0.626         P=0.500        |
|INCIDENTAL TUMOR       |     P=0.329         P=0.669N        P=0.382        |     P=0.366         P=0.634         P=0.500        |
|LOGISTIC REGRESSION    |     P=0.329         P=0.726N        P=0.391        |     P=0.370         P=0.614         P=0.500        |
|COCHRAN-ARMITAGE       |     P=0.254                                        |     P=0.386                                        |
|FISHER EXACT           |                     P=0.697N        P=0.339        |                     P=0.612         P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE   7
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       0/50 (0%)      |     4/50 (8%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            3.1%            0.0%          |     12.4%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       0/27 (0%)       0/32 (0%)      |     2/28 (7%)       0/27 (0%)       0/28 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             690             ---           |      574             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.687N        P=0.534           (e)          |     P=0.016N*       P=0.071N        P=0.065N       |
|INCIDENTAL TUMOR       |     P=0.726N        P=0.479           (e)          |     P=0.014N*       P=0.087N        P=0.058N       |
|LOGISTIC REGRESSION    |     P=0.722N        P=0.506           (e)          |     P=0.016N*       P=0.064N        P=0.068N       |
|COCHRAN-ARMITAGE       |     P=0.730N                                       |     P=0.015N*                                      |
|FISHER EXACT           |                     P=0.500           (e)          |                     P=0.059N        P=0.059N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       0/50 (0%)      |     4/50 (8%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      0.0%            3.1%            0.0%          |     12.4%            0.0%            2.8%          |
|TERMINAL (d)           |     0/24 (0%)       0/27 (0%)       0/32 (0%)      |     2/28 (7%)       0/27 (0%)       0/28 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             690             ---           |      574             ---             668           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.687N        P=0.534           (e)          |     P=0.084N        P=0.071N        P=0.182N       |
|INCIDENTAL TUMOR       |     P=0.726N        P=0.479           (e)          |     P=0.083N        P=0.087N        P=0.190N       |
|LOGISTIC REGRESSION    |     P=0.722N        P=0.506           (e)          |     P=0.086N        P=0.064N        P=0.191N       |
|COCHRAN-ARMITAGE       |     P=0.730N                                       |     P=0.082N                                       |
|FISHER EXACT           |                     P=0.500           (e)          |                     P=0.059N        P=0.181N       |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE   8
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       1/50 (2%)       3/50 (6%)      |    22/50 (44%)     14/50 (28%)      6/50 (12%)     |
|ADJUSTED (b)           |     14.3%            3.7%            8.8%          |     62.0%           41.4%           17.1%          |
|TERMINAL (d)           |     2/24 (8%)       1/27 (4%)       2/32 (6%)      |    15/28 (54%)      8/27 (30%)      2/28 (7%)      |
|FIRST INCIDENCE (DAYS) |      668             729 (T)         695           |      556             682             578           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.293N        P=0.148N        P=0.354N       |     P<0.001N**      P=0.093N        P<0.001N**     |
|INCIDENTAL TUMOR       |     P=0.333N        P=0.171N        P=0.411N       |     P<0.001N**      P=0.088N        P<0.001N**     |
|LOGISTIC REGRESSION    |     P=0.335N        P=0.158N        P=0.415N       |     P<0.001N**      P=0.064N        P<0.001N**     |
|COCHRAN-ARMITAGE       |     P=0.414N                                       |     P<0.001N**                                     |
|FISHER EXACT           |                     P=0.181N        P=0.500N       |                     P=0.072N        P<0.001N**     |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma or Adenoma                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       1/50 (2%)       3/50 (6%)      |    22/50 (44%)     14/50 (28%)      6/50 (12%)     |
|ADJUSTED (b)           |     14.3%            3.7%            8.8%          |     62.0%           41.4%           17.1%          |
|TERMINAL (d)           |     2/24 (8%)       1/27 (4%)       2/32 (6%)      |    15/28 (54%)      8/27 (30%)      2/28 (7%)      |
|FIRST INCIDENCE (DAYS) |      668             729 (T)         695           |      556             682             578           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.293N        P=0.148N        P=0.354N       |     P<0.001N**      P=0.093N        P<0.001N**     |
|INCIDENTAL TUMOR       |     P=0.333N        P=0.171N        P=0.411N       |     P<0.001N**      P=0.088N        P<0.001N**     |
|LOGISTIC REGRESSION    |     P=0.335N        P=0.158N        P=0.415N       |     P<0.001N**      P=0.064N        P<0.001N**     |
|COCHRAN-ARMITAGE       |     P=0.414N                                       |     P<0.001N**                                     |
|FISHER EXACT           |                     P=0.181N        P=0.500N       |                     P=0.072N        P<0.001N**     |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE   9
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       2/50 (4%)       3/50 (6%)      |    24/50 (48%)     14/50 (28%)      6/50 (12%)     |
|ADJUSTED (b)           |     14.3%            6.7%            8.8%          |     67.9%           41.4%           17.1%          |
|TERMINAL (d)           |     2/24 (8%)       1/27 (4%)       2/32 (6%)      |    17/28 (61%)      8/27 (30%)      2/28 (7%)      |
|FIRST INCIDENCE (DAYS) |      668             690             695           |      556             682             578           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.289N        P=0.283N        P=0.354N       |     P<0.001N**      P=0.045N*       P<0.001N**     |
|INCIDENTAL TUMOR       |     P=0.340N        P=0.332N        P=0.411N       |     P<0.001N**      P=0.039N*       P<0.001N**     |
|LOGISTIC REGRESSION    |     P=0.340N        P=0.309N        P=0.415N       |     P<0.001N**      P=0.025N*       P<0.001N**     |
|COCHRAN-ARMITAGE       |     P=0.418N                                       |     P<0.001N**                                     |
|FISHER EXACT           |                     P=0.339N        P=0.500N       |                     P=0.032N*       P<0.001N**     |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Lip)                                                                           |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       0/50 (0%)      |     0/50 (0%)       2/50 (4%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            3.7%            0.0%          |      0.0%            5.7%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       1/27 (4%)       0/32 (0%)      |     0/28 (0%)       0/27 (0%)       0/28 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             729 (T)         ---           |      ---             689             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.689N        P=0.523           (e)          |     P=0.664         P=0.263           (e)          |
|INCIDENTAL TUMOR       |     P=0.689N        P=0.523           (e)          |     P=0.602         P=0.252           (e)          |
|LOGISTIC REGRESSION    |     P=0.689N        P=0.523           (e)          |     P=0.658         P=0.235           (e)          |
|COCHRAN-ARMITAGE       |     P=0.730N                                       |     P=0.669                                        |
|FISHER EXACT           |                     P=0.500           (e)          |                     P=0.247           (e)          |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE  10
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     7/50 (14%)      0/22 (0%)       5/50 (10%)     |     2/49 (4%)       0/24 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |     26.9%            0.0%           14.9%          |      7.1%            0.0%            0.0%          |
|TERMINAL (d)           |     5/24 (21%)      0/1 (0%)        4/32 (13%)     |     2/28 (7%)       0/1 (0%)        0/28 (0%)      |
|FIRST INCIDENCE (DAYS) |      708             ---             695           |      730 (T)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.160N        P=0.168N        P=0.200N       |     P=0.140N        P=0.956N        P=0.238N       |
|INCIDENTAL TUMOR       |     P=0.184N        P=0.228N        P=0.237N       |     P=0.140N        P=0.956N        P=0.238N       |
|LOGISTIC REGRESSION    |     P=0.156N        P=0.307N        P=0.203N       |     P=0.140N        P=0.956N        P=0.238N       |
|COCHRAN-ARMITAGE       |     P=0.309N                                       |     P=0.114N                                       |
|FISHER EXACT           |                     P=0.068N        P=0.380N       |                     P=0.447N        P=0.242N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    11/48 (23%)     11/28 (39%)     16/49 (33%)     |    22/49 (45%)     24/37 (65%)     16/48 (33%)     |
|ADJUSTED (b)           |     37.4%           72.8%           41.7%          |     63.7%           77.1%           44.1%          |
|TERMINAL (d)           |     7/24 (29%)      4/6 (67%)      10/31 (32%)     |    16/28 (57%)     10/15 (67%)      8/27 (30%)     |
|FIRST INCIDENCE (DAYS) |      577             489             414           |      512             287             578           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.424         P=0.098         P=0.425        |     P=0.208N        P=0.057         P=0.202N       |
|INCIDENTAL TUMOR       |     P=0.221         P=0.043 *       P=0.239        |     P=0.262N        P=0.042 *       P=0.273N       |
|LOGISTIC REGRESSION    |     P=0.222         P=0.040 *       P=0.234        |     P=0.211N        P=0.036 *       P=0.237N       |
|COCHRAN-ARMITAGE       |     P=0.178                                        |     P=0.153N                                       |
|FISHER EXACT           |                     P=0.105         P=0.200        |                     P=0.052         P=0.169N       |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE  11
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    12/48 (25%)     12/28 (43%)     16/49 (33%)     |    22/49 (45%)     24/37 (65%)     16/48 (33%)     |
|ADJUSTED (b)           |     38.9%           73.3%           41.7%          |     63.7%           77.1%           44.1%          |
|TERMINAL (d)           |     7/24 (29%)      4/6 (67%)      10/31 (32%)     |    16/28 (57%)     10/15 (67%)      8/27 (30%)     |
|FIRST INCIDENCE (DAYS) |      575             399             414           |      512             287             578           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.507         P=0.112         P=0.514        |     P=0.208N        P=0.057         P=0.202N       |
|INCIDENTAL TUMOR       |     P=0.263         P=0.050         P=0.294        |     P=0.262N        P=0.042 *       P=0.273N       |
|LOGISTIC REGRESSION    |     P=0.268         P=0.053         P=0.299        |     P=0.211N        P=0.036 *       P=0.237N       |
|COCHRAN-ARMITAGE       |     P=0.246                                        |     P=0.153N                                       |
|FISHER EXACT           |                     P=0.088         P=0.272        |                     P=0.052         P=0.169N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal Cell Adenoma                                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       4/50 (8%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%           14.8%            0.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       4/27 (15%)      0/32 (0%)      |     0/28 (0%)       0/27 (0%)       0/28 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             729 (T)         ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.526N        P=0.077           (e)          |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.526N        P=0.077           (e)          |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.526N        P=0.077           (e)          |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.619N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.059           (e)          |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE  12
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       4/50 (8%)       6/50 (12%)     |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      4.2%           14.8%           18.8%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/24 (4%)       4/27 (15%)      6/32 (19%)     |     0/28 (0%)       0/27 (0%)       0/28 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         729 (T)       |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.088         P=0.213         P=0.112        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.088         P=0.213         P=0.112        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.088         P=0.213         P=0.112        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.042 *                                      |       (e)                                          |
|FISHER EXACT           |                     P=0.181         P=0.056        |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Basal Cell Carcinoma, or Basal Cell Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       4/50 (8%)       1/50 (2%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%           14.8%            3.1%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       4/27 (15%)      1/32 (3%)      |     0/28 (0%)       0/27 (0%)       0/28 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             729 (T)         729 (T)       |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.499         P=0.077         P=0.557        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.499         P=0.077         P=0.557        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.499         P=0.077         P=0.557        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.393                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.059         P=0.500        |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE  13
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       8/50 (16%)      7/50 (14%)     |     1/50 (2%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      4.2%           29.6%           21.9%          |      3.3%            0.0%            2.9%          |
|TERMINAL (d)           |     1/24 (4%)       8/27 (30%)      7/32 (22%)     |     0/28 (0%)       0/27 (0%)       0/28 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         729 (T)       |      716             ---             669           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.091         P=0.023 *       P=0.070        |     P=0.666N        P=0.514N        P=0.757N       |
|INCIDENTAL TUMOR       |     P=0.091         P=0.023 *       P=0.070        |     P=0.602         P=0.485N        P=0.680        |
|LOGISTIC REGRESSION    |     P=0.091         P=0.023 *       P=0.068        |     P=0.659         P=0.497N        P=0.752        |
|COCHRAN-ARMITAGE       |     P=0.038 *                                      |     P=0.669N                                       |
|FISHER EXACT           |                     P=0.015 *       P=0.030 *      |                     P=0.500N        P=0.753N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       6/50 (12%)      4/50 (8%)      |     1/50 (2%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |     11.9%           19.6%           10.9%          |      3.3%            3.7%            0.0%          |
|TERMINAL (d)           |     2/24 (8%)       4/27 (15%)      2/32 (6%)      |     0/28 (0%)       1/27 (4%)       0/28 (0%)      |
|FIRST INCIDENCE (DAYS) |      708             555             663           |      716             730 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.547N        P=0.308         P=0.643        |     P=0.334N        P=0.749         P=0.500N       |
|INCIDENTAL TUMOR       |     P=0.514         P=0.264         P=0.589        |     P=0.365N        P=0.756N        P=0.573N       |
|LOGISTIC REGRESSION    |     P=0.511         P=0.273         P=0.586        |     P=0.338N        P=0.758N        P=0.510N       |
|COCHRAN-ARMITAGE       |     P=0.431                                        |     P=0.331N                                       |
|FISHER EXACT           |                     P=0.243         P=0.500        |                     P=0.753N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE  14
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       0/50 (0%)       0/50 (0%)      |     0/50 (0%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |     13.0%            0.0%            0.0%          |      0.0%            2.7%            2.9%          |
|TERMINAL (d)           |     2/24 (8%)       0/27 (0%)       0/32 (0%)      |     0/28 (0%)       0/27 (0%)       0/28 (0%)      |
|FIRST INCIDENCE (DAYS) |      574             ---             ---           |      ---             689             670           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.011N*       P=0.058N        P=0.043N*      |     P=0.321         P=0.529         P=0.500        |
|INCIDENTAL TUMOR       |     P=0.017N*       P=0.062N        P=0.077N       |     P=0.252         P=0.515         P=0.427        |
|LOGISTIC REGRESSION    |     P=0.015N*       P=0.063N        P=0.066N       |     P=0.324         P=0.498         P=0.496        |
|COCHRAN-ARMITAGE       |     P=0.015N*                                      |     P=0.331                                        |
|FISHER EXACT           |                     P=0.059N        P=0.059N       |                     P=0.500         P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Lipoma                                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            6.3%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       0/27 (0%)       2/32 (6%)      |     0/28 (0%)       0/27 (0%)       0/28 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             729 (T)       |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.127           (e)           P=0.303        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.127           (e)           P=0.303        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.127           (e)           P=0.303        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.095                                        |       (e)                                          |
|FISHER EXACT           |                       (e)           P=0.247        |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE  15
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     7/50 (14%)      6/50 (12%)      4/50 (8%)      |     1/50 (2%)       3/50 (6%)       2/50 (4%)      |
|ADJUSTED (b)           |     24.0%           19.6%           10.9%          |      3.3%            8.6%            5.5%          |
|TERMINAL (d)           |     4/24 (17%)      4/27 (15%)      2/32 (6%)      |     0/28 (0%)       1/27 (4%)       0/28 (0%)      |
|FIRST INCIDENCE (DAYS) |      574             555             663           |      716             678             599           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.114N        P=0.422N        P=0.149N       |     P=0.385         P=0.326         P=0.491        |
|INCIDENTAL TUMOR       |     P=0.178N        P=0.478N        P=0.232N       |     P=0.354         P=0.320         P=0.478        |
|LOGISTIC REGRESSION    |     P=0.171N        P=0.472N        P=0.219N       |     P=0.386         P=0.302         P=0.500        |
|COCHRAN-ARMITAGE       |     P=0.215N                                       |     P=0.399                                        |
|FISHER EXACT           |                     P=0.500N        P=0.262N       |                     P=0.309         P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       0/50 (0%)       0/50 (0%)      |     0/50 (0%)       2/50 (4%)       2/50 (4%)      |
|ADJUSTED (b)           |     13.0%            0.0%            0.0%          |      0.0%            5.1%            5.5%          |
|TERMINAL (d)           |     2/24 (8%)       0/27 (0%)       0/32 (0%)      |     0/28 (0%)       0/27 (0%)       0/28 (0%)      |
|FIRST INCIDENCE (DAYS) |      574             ---             ---           |      ---             678             599           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.011N*       P=0.058N        P=0.043N*      |     P=0.161         P=0.274         P=0.231        |
|INCIDENTAL TUMOR       |     P=0.017N*       P=0.062N        P=0.077N       |     P=0.155         P=0.252         P=0.254        |
|LOGISTIC REGRESSION    |     P=0.015N*       P=0.063N        P=0.066N       |     P=0.169         P=0.236         P=0.247        |
|COCHRAN-ARMITAGE       |     P=0.015N*                                      |     P=0.176                                        |
|FISHER EXACT           |                     P=0.059N        P=0.059N       |                     P=0.247         P=0.247        |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE  16
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    44/50 (88%)     46/50 (92%)     44/50 (88%)     |                                                    |
|ADJUSTED (b)           |     97.7%          100.0%          100.0%          |                                                    |
|TERMINAL (d)           |    23/24 (96%)     27/27 (100%)    32/32 (100%)    |                                                    |
|FIRST INCIDENCE (DAYS) |      465             381             365           |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.039N*       P=0.422N        P=0.047N*      |                                                    |
|INCIDENTAL TUMOR       |     P=0.198N        P=0.437         P=0.250N       |                                                    |
|LOGISTIC REGRESSION    |     P=0.388N        P=0.325         P=0.249N       |                                                    |
|COCHRAN-ARMITAGE       |     P=0.564N                                       |                                                    |
|FISHER EXACT           |                     P=0.370         P=0.620N       |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     7/50 (14%)      1/25 (4%)       5/50 (10%)     |     7/50 (14%)      2/27 (7%)       3/50 (6%)      |
|ADJUSTED (b)           |     27.0%           33.3%           13.1%          |     23.5%            5.6%           10.7%          |
|TERMINAL (d)           |     6/24 (25%)      1/3 (33%)       2/32 (6%)      |     6/28 (21%)      0/4 (0%)        3/28 (11%)     |
|FIRST INCIDENCE (DAYS) |      596             729 (T)         550           |      667             641             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.172N        P=0.596N        P=0.221N       |     P=0.128N        P=0.580N        P=0.157N       |
|INCIDENTAL TUMOR       |     P=0.225N        P=0.612N        P=0.313N       |     P=0.124N        P=0.633N        P=0.169N       |
|LOGISTIC REGRESSION    |     P=0.230N        P=0.354N        P=0.311N       |     P=0.135N        P=0.485N        P=0.168N       |
|COCHRAN-ARMITAGE       |     P=0.313N                                       |     P=0.116N                                       |
|FISHER EXACT           |                     P=0.180N        P=0.380N       |                     P=0.323N        P=0.159N       |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE  17
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       1/25 (4%)       2/50 (4%)      |     1/50 (2%)       1/27 (4%)       1/50 (2%)      |
|ADJUSTED (b)           |     13.5%           33.3%            6.3%          |      3.6%           25.0%            3.6%          |
|TERMINAL (d)           |     2/24 (8%)       1/3 (33%)       2/32 (6%)      |     1/28 (4%)       1/4 (25%)       1/28 (4%)      |
|FIRST INCIDENCE (DAYS) |      580             729 (T)         729 (T)       |      730 (T)         730 (T)         730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.168N        P=0.560N        P=0.232N       |     P=0.619         P=0.293         P=0.762        |
|INCIDENTAL TUMOR       |     P=0.200N        P=0.600N        P=0.294N       |     P=0.619         P=0.293         P=0.762        |
|LOGISTIC REGRESSION    |     P=0.207N        P=0.529N        P=0.299N       |     P=0.619         P=0.293         P=0.762        |
|COCHRAN-ARMITAGE       |     P=0.258N                                       |     P=0.629                                        |
|FISHER EXACT           |                     P=0.456N        P=0.339N       |                     P=0.581         P=0.753N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    11/50 (22%)      2/25 (8%)       6/50 (12%)     |     8/50 (16%)      3/27 (11%)      4/50 (8%)      |
|ADJUSTED (b)           |     38.7%           66.7%           16.0%          |     27.0%           29.2%           14.3%          |
|TERMINAL (d)           |     8/24 (33%)      2/3 (67%)       3/32 (9%)      |     7/28 (25%)      1/4 (25%)       4/28 (14%)     |
|FIRST INCIDENCE (DAYS) |      580             729 (T)         550           |      667             641             730 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.036N*       P=0.449N        P=0.055N       |     P=0.150N        P=0.506         P=0.174N       |
|INCIDENTAL TUMOR       |     P=0.058N        P=0.491N        P=0.102N       |     P=0.146N        P=0.456         P=0.186N       |
|LOGISTIC REGRESSION    |     P=0.061N        P=0.256N        P=0.102N       |     P=0.160N        P=0.641N        P=0.187N       |
|COCHRAN-ARMITAGE       |     P=0.106N                                       |     P=0.139N                                       |
|FISHER EXACT           |                     P=0.115N        P=0.143N       |                     P=0.414N        P=0.178N       |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE  18
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       1/25 (4%)       0/50 (0%)      |     1/50 (2%)       1/27 (4%)       2/50 (4%)      |
|ADJUSTED (b)           |      4.2%           33.3%            0.0%          |      3.6%           25.0%            6.8%          |
|TERMINAL (d)           |     1/24 (4%)       1/3 (33%)       0/32 (0%)      |     1/28 (4%)       1/4 (25%)       1/28 (4%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         ---           |      730 (T)         730 (T)         726           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.284N        P=0.262         P=0.443N       |     P=0.395         P=0.293         P=0.504        |
|INCIDENTAL TUMOR       |     P=0.284N        P=0.262         P=0.443N       |     P=0.368         P=0.293         P=0.458        |
|LOGISTIC REGRESSION    |     P=0.284N        P=0.262         P=0.443N       |     P=0.397         P=0.293         P=0.498        |
|COCHRAN-ARMITAGE       |     P=0.345N                                       |     P=0.387                                        |
|FISHER EXACT           |                     P=0.559         P=0.500N       |                     P=0.581         P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/25 (4%)       0/50 (0%)      |     1/50 (2%)       1/27 (4%)       2/50 (4%)      |
|ADJUSTED (b)           |      7.7%           33.3%            0.0%          |      3.6%           25.0%            6.8%          |
|TERMINAL (d)           |     1/24 (4%)       1/3 (33%)       0/32 (0%)      |     1/28 (4%)       1/4 (25%)       1/28 (4%)      |
|FIRST INCIDENCE (DAYS) |      700             729 (T)         ---           |      730 (T)         730 (T)         726           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.118N        P=0.651         P=0.179N       |     P=0.395         P=0.293         P=0.504        |
|INCIDENTAL TUMOR       |     P=0.132N        P=0.616         P=0.208N       |     P=0.368         P=0.293         P=0.458        |
|LOGISTIC REGRESSION    |     P=0.123N        P=0.586         P=0.192N       |     P=0.397         P=0.293         P=0.498        |
|COCHRAN-ARMITAGE       |     P=0.164N                                       |     P=0.387                                        |
|FISHER EXACT           |                     P=0.744N        P=0.247N       |                     P=0.581         P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE  19
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |    10/50 (20%)      9/50 (18%)     13/50 (26%)     |
|ADJUSTED (b)           |                                                    |     30.9%           28.4%           42.4%          |
|TERMINAL (d)           |                                                    |     7/28 (25%)      6/27 (22%)     11/28 (39%)     |
|FIRST INCIDENCE (DAYS) |                                                    |      556             501             325           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.263         P=0.510N        P=0.309        |
|INCIDENTAL TUMOR       |                                                    |     P=0.256         P=0.531N        P=0.346        |
|LOGISTIC REGRESSION    |                                                    |     P=0.223         P=0.510N        P=0.262        |
|COCHRAN-ARMITAGE       |                                                    |     P=0.271                                        |
|FISHER EXACT           |                                                    |                     P=0.500N        P=0.318        |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |    11/50 (22%)      9/50 (18%)     13/50 (26%)     |
|ADJUSTED (b)           |                                                    |     34.2%           28.4%           42.4%          |
|TERMINAL (d)           |                                                    |     8/28 (29%)      6/27 (22%)     11/28 (39%)     |
|FIRST INCIDENCE (DAYS) |                                                    |      556             501             325           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.349         P=0.414N        P=0.399        |
|INCIDENTAL TUMOR       |                                                    |     P=0.344         P=0.433N        P=0.441        |
|LOGISTIC REGRESSION    |                                                    |     P=0.303         P=0.409N        P=0.344        |
|COCHRAN-ARMITAGE       |                                                    |     P=0.359                                        |
|FISHER EXACT           |                                                    |                     P=0.402N        P=0.408        |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE  20
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       0/50 (0%)       1/50 (2%)      |     0/50 (0%)       2/50 (4%)       1/50 (2%)      |
|ADJUSTED (b)           |      2.0%            0.0%            2.5%          |      0.0%            4.8%            2.3%          |
|TERMINAL (d)           |     0/24 (0%)       0/27 (0%)       0/32 (0%)      |     0/28 (0%)       0/27 (0%)       0/28 (0%)      |
|FIRST INCIDENCE (DAYS) |      465             ---             667           |      ---             337             574           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.646N        P=0.512N        P=0.737N       |     P=0.350         P=0.250         P=0.505        |
|INCIDENTAL TUMOR       |     P=0.561         P=0.531N        P=0.634        |     P=0.535         P=0.323         P=0.612        |
|LOGISTIC REGRESSION    |     P=0.647         P=0.355N        P=0.738        |     P=0.479         P=0.309         P=0.550        |
|COCHRAN-ARMITAGE       |     P=0.668                                        |     P=0.360                                        |
|FISHER EXACT           |                     P=0.500N        P=0.753N       |                     P=0.247         P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |      4.2%            0.0%            0.0%          |      0.0%            0.0%            5.7%          |
|TERMINAL (d)           |     1/24 (4%)       0/27 (0%)       0/32 (0%)      |     0/28 (0%)       0/27 (0%)       1/28 (4%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         ---             ---           |      ---             ---             452           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.234N        P=0.477N        P=0.443N       |     P=0.094           (e)           P=0.230        |
|INCIDENTAL TUMOR       |     P=0.234N        P=0.477N        P=0.443N       |     P=0.042 *         (e)           P=0.106        |
|LOGISTIC REGRESSION    |     P=0.234N        P=0.477N        P=0.443N       |     P=0.110           (e)           P=0.270        |
|COCHRAN-ARMITAGE       |     P=0.271N                                       |     P=0.095                                        |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                       (e)           P=0.247        |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE  21
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |      4.2%            0.0%            0.0%          |      0.0%            0.0%            5.7%          |
|TERMINAL (d)           |     1/24 (4%)       0/27 (0%)       0/32 (0%)      |     0/28 (0%)       0/27 (0%)       1/28 (4%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         ---             ---           |      ---             ---             452           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.234N        P=0.477N        P=0.443N       |     P=0.094           (e)           P=0.230        |
|INCIDENTAL TUMOR       |     P=0.234N        P=0.477N        P=0.443N       |     P=0.042 *         (e)           P=0.106        |
|LOGISTIC REGRESSION    |     P=0.234N        P=0.477N        P=0.443N       |     P=0.110           (e)           P=0.270        |
|COCHRAN-ARMITAGE       |     P=0.271N                                       |     P=0.095                                        |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                       (e)           P=0.247        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    16/50 (32%)     15/50 (30%)      9/50 (18%)     |    13/50 (26%)      9/50 (18%)     11/50 (22%)     |
|ADJUSTED (b)           |     44.9%           43.9%           23.2%          |     31.3%           26.5%           30.7%          |
|TERMINAL (d)           |     7/24 (29%)      9/27 (33%)      4/32 (13%)     |     3/28 (11%)      5/27 (19%)      4/28 (14%)     |
|FIRST INCIDENCE (DAYS) |      469             533             577           |      498             569             596           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.023N*       P=0.383N        P=0.033N*      |     P=0.392N        P=0.252N        P=0.443N       |
|INCIDENTAL TUMOR       |     P=0.078N        P=0.497N        P=0.131N       |     P=0.469N        P=0.271N        P=0.502        |
|LOGISTIC REGRESSION    |     P=0.063N        P=0.492N        P=0.096N       |     P=0.451N        P=0.450N        P=0.417N       |
|COCHRAN-ARMITAGE       |     P=0.071N                                       |     P=0.359N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.083N       |                     P=0.235N        P=0.408N       |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE  22
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma Benign, Malignant, NOS                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       4/50 (8%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            2.4%           10.7%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/24 (0%)       0/27 (0%)       1/32 (3%)      |     0/28 (0%)       0/27 (0%)       0/28 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             588             529           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.044 *       P=0.520         P=0.104        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.013 *       P=0.477         P=0.035 *      |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.023 *       P=0.510         P=0.062        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.026 *                                      |       (e)                                          |
|FISHER EXACT           |                     P=0.500         P=0.059        |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    46/50 (92%)     48/50 (96%)     50/50 (100%)    |    38/50 (76%)     42/50 (84%)     33/50 (66%)     |
|ADJUSTED (b)           |    100.0%          100.0%          100.0%          |     92.5%           91.3%           86.5%          |
|TERMINAL (d)           |    24/24 (100%)    27/27 (100%)    32/32 (100%)    |    25/28 (89%)     23/27 (85%)     23/28 (82%)     |
|FIRST INCIDENCE (DAYS) |      465             381             365           |      512             287             325           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.135N        P=0.409N        P=0.153N       |     P=0.249N        P=0.292         P=0.249N       |
|INCIDENTAL TUMOR       |     P=0.136         P=0.397         P=0.220        |     P=0.245N        P=0.174         P=0.227N       |
|LOGISTIC REGRESSION    |     P=0.017 *       P=0.174         P=0.062        |     P=0.293N        P=0.142         P=0.336N       |
|COCHRAN-ARMITAGE       |     P=0.037 *                                      |     P=0.148N                                       |
|FISHER EXACT           |                     P=0.339         P=0.059        |                     P=0.227         P=0.189N       |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE  23
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      VEHICLE         112.            225.          |      VEHICLE         225.            450.          |
|                       |      CONTROL         MG/KG           MG/KG         |      CONTROL         MG/KG           MG/KG         |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    30/50 (60%)     30/50 (60%)     23/50 (46%)     |    22/50 (44%)     19/50 (38%)     19/50 (38%)     |
|ADJUSTED (b)           |     69.7%           65.9%           51.5%          |     52.0%           46.2%           47.9%          |
|TERMINAL (d)           |    12/24 (50%)     12/27 (44%)     11/32 (34%)     |     9/28 (32%)      7/27 (26%)      8/28 (29%)     |
|FIRST INCIDENCE (DAYS) |      465             392             529           |      498             337             452           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.032N*       P=0.412N        P=0.037N*      |     P=0.367N        P=0.365N        P=0.396N       |
|INCIDENTAL TUMOR       |     P=0.230N        P=0.519         P=0.254N       |     P=0.422N        P=0.358N        P=0.560        |
|LOGISTIC REGRESSION    |     P=0.264N        P=0.431         P=0.298N       |     P=0.465N        P=0.480N        P=0.511N       |
|COCHRAN-ARMITAGE       |     P=0.095N                                       |     P=0.305N                                       |
|FISHER EXACT           |                     P=0.581N        P=0.115N       |                     P=0.342N        P=0.342N       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    50/50 (100%)    50/50 (100%)    50/50 (100%)    |    46/50 (92%)     46/50 (92%)     41/50 (82%)     |
|ADJUSTED (b)           |    100.0%          100.0%          100.0%          |     95.8%           93.9%           91.1%          |
|TERMINAL (d)           |    24/24 (100%)    27/27 (100%)    32/32 (100%)    |    26/28 (93%)     24/27 (89%)     24/28 (86%)     |
|FIRST INCIDENCE (DAYS) |      465             381             365           |      498             287             325           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.048N*       P=0.309N        P=0.055N       |     P=0.287N        P=0.532         P=0.300N       |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.225N        P=0.588         P=0.419N       |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.187N        P=0.612         P=0.297N       |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.078N                                       |
|FISHER EXACT           |                     P=1.000N        P=1.000N       |                     P=0.643N        P=0.117N       |
|=================================================================================================================================|
 
         DATE: 09/02/94                     EXPERIMENT: 05002 TEST: 05                                                 PAGE  24
                           STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- GAMMA-BUTYROLACTONE
 
                                                 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.
 (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.