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TR 391 Rat Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Microbiological Assoc.                           TRIS 2-CHLOROETHYL PHOSPHATE                             DATE: 09/05/94       
EXPERIMENT: 05042 TEST: 01                                                                                     TIME: 15:05:52       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01CP9565001          ROUTE: GAVAGE                                                                      NTP C#: 60128        
PATHOLOGIST: G. PARKER                                                                                         CAS: 115-96-8        
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: Microbiological Assoc.                           TRIS 2-CHLOROETHYL PHOSPHATE                             DATE: 09/05/94      
EXPERIMENT: 05042 TEST: 01                                                                                     TIME: 15:05:52      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01CP9565001          ROUTE: GAVAGE                                                                      NTP C#: 60128       
PATHOLOGIST: G. PARKER                                                                                         CAS: 115-96-8       
 
 
 
 
 
                                                    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: Microbiological Assoc.                           TRIS 2-CHLOROETHYL PHOSPHATE                             DATE: 09/05/94       
EXPERIMENT: 05042 TEST: 01                                                                                     TIME: 15:05:52       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01CP9565001          ROUTE: GAVAGE                                                                      NTP C#: 60128        
PATHOLOGIST: G. PARKER                                                                                         CAS: 115-96-8        
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                  IN THE ANALYSIS OF THE STUDY OF TRIS 2-CHLOROETHYL PHOSPHATE
 
              ====================================================================================================
 
                                                           MALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Adrenal Medulla               Pheochromocytoma Benign
                                                           Pheochromocytoma: Benign, Complex, Malignant, NOS
                             Brain                         Granular Cell Tumor Benign
                             Kidney: Renal Tubule          Adenoma
                                                           Carcinoma or Adenoma
                             Skin: Subcutaneous Tissue     Fibroma
                             Testes                        Adenoma
                             Thyroid Gland: C-Cell         Adenoma
                                                           Carcinoma or Adenoma
                             Thyroid Gland: Follicular Cell
                                                           Carcinoma or Adenoma
                             All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear,
                                                            or Undifferentiated
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Kidney: Renal Tubule          Adenoma
                                                           Carcinoma or Adenoma
                             Mammary Gland                 Fibroadenoma
                                                           Fibroma, Fibroadenoma or Adenoma
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             Thyroid Gland: Follicular Cell
                                                           Carcinoma
                                                           Carcinoma or Adenoma
                             Uterus                        Sarcoma Stromal
                                                           Sarcoma Stromal or Polyp Stromal
                             All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear,
                                                            or Undifferentiated
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE   1
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    10/43 (23%)     21/47 (45%)     13/44 (30%)     |     0/43 (0%)       2/41 (5%)       0/45 (0%)      |
|ADJUSTED (b)           |     33.3%           57.8%           43.5%          |      0.0%            6.9%            0.0%          |
|TERMINAL (d)           |    10/30 (33%)     17/32 (53%)      8/23 (35%)     |     0/28 (0%)       2/29 (7%)       0/16 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         603             528           |      ---             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.100         P=0.020 *       P=0.137        |     P=0.562         P=0.246           (e)          |
|INCIDENTAL TUMOR       |     P=0.347         P=0.056         P=0.355        |     P=0.562         P=0.246           (e)          |
|LOGISTIC REGRESSION    |     P=0.305         P=0.037 *       P=0.341        |     P=0.562         P=0.246           (e)          |
|COCHRAN-ARMITAGE       |     P=0.308                                        |     P=0.661N                                       |
|FISHER EXACT           |                     P=0.027 *       P=0.337        |                     P=0.235           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Malignant                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/43 (5%)       1/47 (2%)       5/44 (11%)     |     0/43 (0%)       0/41 (0%)       0/45 (0%)      |
|ADJUSTED (b)           |      5.9%            3.1%           21.7%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/30 (3%)       1/32 (3%)       5/23 (22%)     |     0/28 (0%)       0/29 (0%)       0/16 (0%)      |
|FIRST INCIDENCE (DAYS) |      641             729 (T)         729 (T)       |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.079         P=0.482N        P=0.135        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.092         P=0.421N        P=0.162        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.118         P=0.448N        P=0.204        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.136                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.466N        P=0.226        |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE   2
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    12/43 (28%)     22/47 (47%)     17/44 (39%)     |     0/43 (0%)       2/41 (5%)       0/45 (0%)      |
|ADJUSTED (b)           |     38.4%           60.6%           58.6%          |      0.0%            6.9%            0.0%          |
|TERMINAL (d)           |    11/30 (37%)     18/32 (56%)     12/23 (52%)     |     0/28 (0%)       2/29 (7%)       0/16 (0%)      |
|FIRST INCIDENCE (DAYS) |      641             603             528           |      ---             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.036 *       P=0.040 *       P=0.051        |     P=0.562         P=0.246           (e)          |
|INCIDENTAL TUMOR       |     P=0.173         P=0.107         P=0.174        |     P=0.562         P=0.246           (e)          |
|LOGISTIC REGRESSION    |     P=0.170         P=0.073         P=0.199        |     P=0.562         P=0.246           (e)          |
|COCHRAN-ARMITAGE       |     P=0.180                                        |     P=0.661N                                       |
|FISHER EXACT           |                     P=0.051         P=0.202        |                     P=0.235           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Osteosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       2/50 (4%)       0/50 (0%)      |     0/50 (0%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |      0.0%            5.0%            0.0%          |      0.0%            2.5%            2.3%          |
|TERMINAL (d)           |     0/36 (0%)       0/33 (0%)       0/25 (0%)      |     0/32 (0%)       0/33 (0%)       0/17 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             540             ---           |      ---             652             492           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.644         P=0.248           (e)          |     P=0.290         P=0.505         P=0.500        |
|INCIDENTAL TUMOR       |     P=0.517N        P=0.362           (e)          |     P=0.529         P=0.500         P=0.718        |
|LOGISTIC REGRESSION    |     P=0.640         P=0.202           (e)          |     P=0.354         P=0.502         P=0.538        |
|COCHRAN-ARMITAGE       |     P=0.667                                        |     P=0.332                                        |
|FISHER EXACT           |                     P=0.247           (e)          |                     P=0.500         P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE   3
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Brain                                                                                                                            |
|     Granular Cell Tumor Benign                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/49 (0%)       3/50 (6%)      |     0/50 (0%)       2/50 (4%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            9.5%          |      0.0%            6.1%            0.0%          |
|TERMINAL (d)           |     0/36 (0%)       0/32 (0%)       1/25 (4%)      |     0/32 (0%)       2/33 (6%)       0/17 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             575           |      ---             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.028 *         (e)           P=0.094        |     P=0.549         P=0.245           (e)          |
|INCIDENTAL TUMOR       |     P=0.073           (e)           P=0.246        |     P=0.549         P=0.245           (e)          |
|LOGISTIC REGRESSION    |     P=0.037 *         (e)           P=0.119        |     P=0.549         P=0.245           (e)          |
|COCHRAN-ARMITAGE       |     P=0.038 *                                      |     P=0.667                                        |
|FISHER EXACT           |                       (e)           P=0.121        |                     P=0.247           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/42 (2%)       0/47 (0%)       1/42 (2%)      |     7/34 (21%)      3/35 (9%)       4/32 (13%)     |
|ADJUSTED (b)           |      3.0%            0.0%            4.3%          |     30.4%           11.5%           15.2%          |
|TERMINAL (d)           |     1/33 (3%)       0/31 (0%)       1/23 (4%)      |     7/23 (30%)      2/22 (9%)       0/9 (0%)       |
|FIRST INCIDENCE (DAYS) |      729 (T)         ---             729 (T)       |      729 (T)         686             555           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.598         P=0.512N        P=0.679        |     P=0.565N        P=0.166N        P=0.523        |
|INCIDENTAL TUMOR       |     P=0.598         P=0.512N        P=0.679        |     P=0.295N        P=0.145N        P=0.437N       |
|LOGISTIC REGRESSION    |     P=0.598         P=0.512N        P=0.679        |     P=0.370N        P=0.145N        P=0.534N       |
|COCHRAN-ARMITAGE       |     P=0.671N                                       |     P=0.213N                                       |
|FISHER EXACT           |                     P=0.472N        P=0.753N       |                     P=0.141N        P=0.292N       |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE   4
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/42 (7%)       7/47 (15%)      6/42 (14%)     |     2/34 (6%)       4/35 (11%)      2/32 (6%)      |
|ADJUSTED (b)           |      9.1%           17.2%           17.6%          |      5.3%           15.5%            5.2%          |
|TERMINAL (d)           |     3/33 (9%)       2/31 (6%)       1/23 (4%)      |     0/23 (0%)       3/22 (14%)      0/9 (0%)       |
|FIRST INCIDENCE (DAYS) |      729 (T)         441             575           |      634             310             519           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.148         P=0.165         P=0.165        |     P=0.376         P=0.325         P=0.573        |
|INCIDENTAL TUMOR       |     P=0.536         P=0.334         P=0.662        |     P=0.542N        P=0.443         P=0.334N       |
|LOGISTIC REGRESSION    |     P=0.195         P=0.192         P=0.239        |     P=0.589         P=0.356         P=0.688N       |
|COCHRAN-ARMITAGE       |     P=0.202                                        |     P=0.561                                        |
|FISHER EXACT           |                     P=0.208         P=0.241        |                     P=0.351         P=0.670        |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/42 (10%)      7/47 (15%)      7/42 (17%)     |     9/34 (26%)      7/35 (20%)      6/32 (19%)     |
|ADJUSTED (b)           |     12.1%           17.2%           21.4%          |     34.1%           26.4%           19.7%          |
|TERMINAL (d)           |     4/33 (12%)      2/31 (6%)       2/23 (9%)      |     7/23 (30%)      5/22 (23%)      0/9 (0%)       |
|FIRST INCIDENCE (DAYS) |      729 (T)         441             575           |      634             310             519           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.145         P=0.263         P=0.157        |     P=0.427         P=0.423N        P=0.447        |
|INCIDENTAL TUMOR       |     P=0.502         P=0.474         P=0.590        |     P=0.295N        P=0.314N        P=0.239N       |
|LOGISTIC REGRESSION    |     P=0.211         P=0.316         P=0.253        |     P=0.338N        P=0.378N        P=0.467N       |
|COCHRAN-ARMITAGE       |     P=0.214                                        |     P=0.269N                                       |
|FISHER EXACT           |                     P=0.330         P=0.260        |                     P=0.363N        P=0.326N       |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE   5
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart                                                                                                                            |
|     Schwannoma Malignant                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |     2/50 (4%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      5.3%            3.0%            0.0%          |
|TERMINAL (d)           |     0/36 (0%)       0/33 (0%)       0/25 (0%)      |     1/32 (3%)       1/33 (3%)       0/17 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      582             729 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.212N        P=0.493N        P=0.337N       |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.134N        P=0.493N        P=0.192N       |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.153N        P=0.503N        P=0.239N       |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.142N                                       |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.500N        P=0.247N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       2/49 (4%)       3/50 (6%)      |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      2.8%            6.3%           11.4%          |      0.0%            0.0%            5.9%          |
|TERMINAL (d)           |     1/36 (3%)       2/32 (6%)       2/25 (8%)      |     0/32 (0%)       0/33 (0%)       1/17 (6%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         700           |      ---             ---             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.129         P=0.459         P=0.193        |     P=0.184           (e)           P=0.374        |
|INCIDENTAL TUMOR       |     P=0.225         P=0.459         P=0.373        |     P=0.184           (e)           P=0.374        |
|LOGISTIC REGRESSION    |     P=0.168         P=0.459         P=0.253        |     P=0.184           (e)           P=0.374        |
|COCHRAN-ARMITAGE       |     P=0.223                                        |     P=0.271                                        |
|FISHER EXACT           |                     P=0.492         P=0.309        |                       (e)           P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE   6
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       2/49 (4%)       4/50 (8%)      |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      2.8%            6.3%           13.6%          |      0.0%            0.0%            5.9%          |
|TERMINAL (d)           |     1/36 (3%)       2/32 (6%)       2/25 (8%)      |     0/32 (0%)       0/33 (0%)       1/17 (6%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         630           |      ---             ---             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.066         P=0.459         P=0.114        |     P=0.184           (e)           P=0.374        |
|INCIDENTAL TUMOR       |     P=0.129         P=0.459         P=0.249        |     P=0.184           (e)           P=0.374        |
|LOGISTIC REGRESSION    |     P=0.108         P=0.459         P=0.174        |     P=0.184           (e)           P=0.374        |
|COCHRAN-ARMITAGE       |     P=0.119                                        |     P=0.271                                        |
|FISHER EXACT           |                     P=0.492         P=0.181        |                       (e)           P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       5/50 (10%)     24/50 (48%)     |     0/50 (0%)       2/50 (4%)       5/50 (10%)     |
|ADJUSTED (b)           |      2.8%           15.2%           69.7%          |      0.0%            6.1%           29.4%          |
|TERMINAL (d)           |     1/36 (3%)       5/33 (15%)     15/25 (60%)     |     0/32 (0%)       2/33 (6%)       5/17 (29%)     |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         575           |      ---             729 (T)         729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P=0.083         P<0.001 **     |     P=0.001 **      P=0.245         P=0.003 **     |
|INCIDENTAL TUMOR       |     P<0.001 **      P=0.083         P<0.001 **     |     P=0.001 **      P=0.245         P=0.003 **     |
|LOGISTIC REGRESSION    |     P<0.001 **      P=0.083         P<0.001 **     |     P=0.001 **      P=0.245         P=0.003 **     |
|COCHRAN-ARMITAGE       |     P<0.001 **                                     |     P=0.017 *                                      |
|FISHER EXACT           |                     P=0.102         P<0.001 **     |                     P=0.247         P=0.028 *      |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE   7
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       5/50 (10%)     25/50 (50%)     |     0/50 (0%)       2/50 (4%)       5/50 (10%)     |
|ADJUSTED (b)           |      5.6%           15.2%           72.7%          |      0.0%            6.1%           29.4%          |
|TERMINAL (d)           |     2/36 (6%)       5/33 (15%)     16/25 (64%)     |     0/32 (0%)       2/33 (6%)       5/17 (29%)     |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         575           |      ---             729 (T)         729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P=0.181         P<0.001 **     |     P=0.001 **      P=0.245         P=0.003 **     |
|INCIDENTAL TUMOR       |     P<0.001 **      P=0.181         P<0.001 **     |     P=0.001 **      P=0.245         P=0.003 **     |
|LOGISTIC REGRESSION    |     P<0.001 **      P=0.181         P<0.001 **     |     P=0.001 **      P=0.245         P=0.003 **     |
|COCHRAN-ARMITAGE       |     P<0.001 **                                     |     P=0.017 *                                      |
|FISHER EXACT           |                     P=0.218         P<0.001 **     |                     P=0.247         P=0.028 *      |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       2/50 (4%)      |     0/50 (0%)       0/49 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            2.7%            8.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/36 (0%)       0/33 (0%)       2/25 (8%)      |     0/32 (0%)       0/32 (0%)       0/17 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             660             729 (T)       |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.106         P=0.505         P=0.162        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.202           (e)           P=0.162        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.137         P=0.493         P=0.162        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.142                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.500         P=0.247        |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE   8
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       2/50 (4%)      |     0/50 (0%)       0/49 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            2.7%            8.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/36 (0%)       0/33 (0%)       2/25 (8%)      |     0/32 (0%)       0/32 (0%)       0/17 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             660             729 (T)       |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.106         P=0.505         P=0.162        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.202           (e)           P=0.162        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.137         P=0.493         P=0.162        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.142                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.500         P=0.247        |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/49 (0%)       2/50 (4%)      |     1/50 (2%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |      0.0%            0.0%            7.0%          |      3.1%            3.0%            3.0%          |
|TERMINAL (d)           |     0/36 (0%)       0/32 (0%)       1/25 (4%)      |     1/32 (3%)       1/33 (3%)       0/17 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             683           |      729 (T)         729 (T)         596           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.074           (e)           P=0.188        |     P=0.516         P=0.755N        P=0.659        |
|INCIDENTAL TUMOR       |     P=0.166           (e)           P=0.427        |     P=0.642         P=0.755N        P=0.745N       |
|LOGISTIC REGRESSION    |     P=0.093           (e)           P=0.232        |     P=0.613         P=0.755N        P=0.756        |
|COCHRAN-ARMITAGE       |     P=0.097                                        |     P=0.640                                        |
|FISHER EXACT           |                       (e)           P=0.247        |                     P=0.753N        P=0.753N       |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE   9
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |     3/50 (6%)       3/50 (6%)       3/50 (6%)      |
|ADJUSTED (b)           |      2.0%            0.0%            0.0%          |      8.4%            8.3%           13.9%          |
|TERMINAL (d)           |     0/36 (0%)       0/33 (0%)       0/25 (0%)      |     2/32 (6%)       2/33 (6%)       1/17 (6%)      |
|FIRST INCIDENCE (DAYS) |      350             ---             ---           |      597             617             687           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.271N        P=0.500N        P=0.500N       |     P=0.344         P=0.651N        P=0.412        |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.579         P=0.654N        P=0.633        |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.505         P=0.658         P=0.563        |
|COCHRAN-ARMITAGE       |     P=0.270N                                       |     P=0.584                                        |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                     P=0.661N        P=0.661N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |     3/50 (6%)       4/50 (8%)       4/50 (8%)      |
|ADJUSTED (b)           |      2.0%            0.0%            0.0%          |      8.4%           11.3%           19.3%          |
|TERMINAL (d)           |     0/36 (0%)       0/33 (0%)       0/25 (0%)      |     2/32 (6%)       3/33 (9%)       2/17 (12%)     |
|FIRST INCIDENCE (DAYS) |      350             ---             ---           |      597             617             687           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.271N        P=0.500N        P=0.500N       |     P=0.178         P=0.512         P=0.233        |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.358         P=0.512         P=0.415        |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.312         P=0.493         P=0.361        |
|COCHRAN-ARMITAGE       |     P=0.270N                                       |     P=0.424                                        |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                     P=0.500         P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE  10
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       0/50 (0%)      |    17/50 (34%)     21/50 (42%)     18/50 (36%)     |
|ADJUSTED (b)           |      5.6%            3.0%            0.0%          |     45.5%           53.6%           74.0%          |
|TERMINAL (d)           |     2/36 (6%)       1/33 (3%)       0/25 (0%)      |    12/32 (38%)     15/33 (45%)     11/17 (65%)     |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         ---           |      619             588             596           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.201N        P=0.530N        P=0.322N       |     P=0.017 *       P=0.312         P=0.019 *      |
|INCIDENTAL TUMOR       |     P=0.201N        P=0.530N        P=0.322N       |     P=0.160         P=0.293         P=0.158        |
|LOGISTIC REGRESSION    |     P=0.201N        P=0.530N        P=0.322N       |     P=0.089         P=0.253         P=0.084        |
|COCHRAN-ARMITAGE       |     P=0.142N                                       |     P=0.458                                        |
|FISHER EXACT           |                     P=0.500N        P=0.247N       |                     P=0.268         P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma or Adenoma                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       0/50 (0%)      |    17/50 (34%)     22/50 (44%)     18/50 (36%)     |
|ADJUSTED (b)           |      5.6%            3.0%            0.0%          |     45.5%           56.2%           74.0%          |
|TERMINAL (d)           |     2/36 (6%)       1/33 (3%)       0/25 (0%)      |    12/32 (38%)     16/33 (48%)     11/17 (65%)     |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         ---           |      619             588             596           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.201N        P=0.530N        P=0.322N       |     P=0.016 *       P=0.249         P=0.019 *      |
|INCIDENTAL TUMOR       |     P=0.201N        P=0.530N        P=0.322N       |     P=0.150         P=0.226         P=0.158        |
|LOGISTIC REGRESSION    |     P=0.201N        P=0.530N        P=0.322N       |     P=0.083         P=0.190         P=0.084        |
|COCHRAN-ARMITAGE       |     P=0.142N                                       |     P=0.458                                        |
|FISHER EXACT           |                     P=0.500N        P=0.247N       |                     P=0.206         P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE  11
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       1/50 (2%)       0/50 (0%)      |    20/50 (40%)     24/50 (48%)     18/50 (36%)     |
|ADJUSTED (b)           |      7.4%            3.0%            0.0%          |     52.1%           59.7%           74.0%          |
|TERMINAL (d)           |     2/36 (6%)       1/33 (3%)       0/25 (0%)      |    14/32 (44%)     17/33 (52%)     11/17 (65%)     |
|FIRST INCIDENCE (DAYS) |      350             729 (T)         ---           |      597             588             596           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.089N        P=0.330N        P=0.168N       |     P=0.052         P=0.323         P=0.059        |
|INCIDENTAL TUMOR       |     P=0.201N        P=0.530N        P=0.322N       |     P=0.379         P=0.299         P=0.370        |
|LOGISTIC REGRESSION    |     P=0.070N        P=0.342N        P=0.144N       |     P=0.258         P=0.251         P=0.252        |
|COCHRAN-ARMITAGE       |     P=0.060N                                       |     P=0.382N                                       |
|FISHER EXACT           |                     P=0.309N        P=0.121N       |                     P=0.273         P=0.418N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    19/49 (39%)     16/46 (35%)     14/48 (29%)     |    21/49 (43%)     14/49 (29%)     11/47 (23%)     |
|ADJUSTED (b)           |     44.8%           41.4%           42.8%          |     57.9%           38.1%           47.6%          |
|TERMINAL (d)           |    13/36 (36%)     11/33 (33%)      8/25 (32%)     |    16/31 (52%)     11/33 (33%)      6/16 (38%)     |
|FIRST INCIDENCE (DAYS) |      403             506             471           |      633             598             492           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.440N        P=0.403N        P=0.477N       |     P=0.342N        P=0.081N        P=0.500N       |
|INCIDENTAL TUMOR       |     P=0.116N        P=0.282N        P=0.197N       |     P=0.075N        P=0.083N        P=0.145N       |
|LOGISTIC REGRESSION    |     P=0.182N        P=0.421N        P=0.213N       |     P=0.095N        P=0.091N        P=0.165N       |
|COCHRAN-ARMITAGE       |     P=0.187N                                       |     P=0.026N*                                      |
|FISHER EXACT           |                     P=0.425N        P=0.217N       |                     P=0.103N        P=0.035N*      |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE  12
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/49 (4%)       0/46 (0%)       0/48 (0%)      |     1/49 (2%)       2/49 (4%)       0/47 (0%)      |
|ADJUSTED (b)           |      4.4%            0.0%            0.0%          |      2.1%            5.9%            0.0%          |
|TERMINAL (d)           |     0/36 (0%)       0/33 (0%)       0/25 (0%)      |     0/31 (0%)       1/33 (3%)       0/16 (0%)      |
|FIRST INCIDENCE (DAYS) |      419             ---             ---           |      403             724             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.089N        P=0.224N        P=0.226N       |     P=0.462N        P=0.506         P=0.500N       |
|INCIDENTAL TUMOR       |     P=0.189N        P=0.397N        P=0.397N       |     P=0.274N        P=0.247         P=0.282N       |
|LOGISTIC REGRESSION    |     P=0.257N        P=0.502N        P=0.484N       |     P=0.357N        P=0.513         P=0.463N       |
|COCHRAN-ARMITAGE       |     P=0.099N                                       |     P=0.373N                                       |
|FISHER EXACT           |                     P=0.263N        P=0.253N       |                     P=0.500         P=0.510N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    21/49 (43%)     16/46 (35%)     14/48 (29%)     |    22/49 (45%)     16/49 (33%)     11/47 (23%)     |
|ADJUSTED (b)           |     47.2%           41.4%           42.8%          |     58.8%           42.7%           47.6%          |
|TERMINAL (d)           |    13/36 (36%)     11/33 (33%)      8/25 (32%)     |    16/31 (52%)     12/33 (36%)      6/16 (38%)     |
|FIRST INCIDENCE (DAYS) |      403             506             471           |      403             598             492           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.292N        P=0.266N        P=0.327N       |     P=0.297N        P=0.125N        P=0.414N       |
|INCIDENTAL TUMOR       |     P=0.064N        P=0.194N        P=0.125N       |     P=0.043N*       P=0.172N        P=0.082N       |
|LOGISTIC REGRESSION    |     P=0.102N        P=0.314N        P=0.127N       |     P=0.056N        P=0.147N        P=0.082N       |
|COCHRAN-ARMITAGE       |     P=0.096N                                       |     P=0.017N*                                      |
|FISHER EXACT           |                     P=0.276N        P=0.116N       |                     P=0.150N        P=0.022N*      |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE  13
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       3/50 (6%)       2/50 (4%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            9.1%            7.1%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/36 (0%)       3/33 (9%)       0/25 (0%)      |     0/32 (0%)       0/33 (0%)       0/17 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             729 (T)         696           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.126         P=0.106         P=0.183        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.392         P=0.106           (e)          |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.178         P=0.106         P=0.237        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.201                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.121         P=0.247        |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       2/50 (4%)       1/50 (2%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            6.1%            2.2%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/36 (0%)       2/33 (6%)       0/25 (0%)      |     0/32 (0%)       0/33 (0%)       0/17 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             729 (T)         550           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.308         P=0.219         P=0.528        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.332         P=0.219         P=0.594        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.357         P=0.219         P=0.415        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.360                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.247         P=0.500        |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE  14
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       2/50 (4%)       1/50 (2%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      2.8%            6.1%            2.2%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/36 (3%)       2/33 (6%)       0/25 (0%)      |     0/32 (0%)       0/33 (0%)       0/17 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         550           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.549         P=0.470         P=0.737        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.574         P=0.470         P=0.754N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.622N        P=0.470         P=0.752        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.622                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.500         P=0.753N       |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       6/50 (12%)      4/50 (8%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.6%           18.2%           12.8%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     2/36 (6%)       6/33 (18%)      1/25 (4%)      |     0/32 (0%)       0/33 (0%)       0/17 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         550           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.157         P=0.105         P=0.234        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.348         P=0.105         P=0.639        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.273         P=0.105         P=0.340        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.289                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.134         P=0.339        |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE  15
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       3/50 (6%)       6/50 (12%)     |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      2.8%            9.1%           19.1%          |      3.1%            0.0%            0.0%          |
|TERMINAL (d)           |     1/36 (3%)       3/33 (9%)       2/25 (8%)      |     1/32 (3%)       0/33 (0%)       0/17 (0%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         729 (T)         674           |      729 (T)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.016 *       P=0.274         P=0.033 *      |     P=0.337N        P=0.494N        P=0.626N       |
|INCIDENTAL TUMOR       |     P=0.132         P=0.274         P=0.373        |     P=0.337N        P=0.494N        P=0.626N       |
|LOGISTIC REGRESSION    |     P=0.030 *       P=0.274         P=0.055        |     P=0.337N        P=0.494N        P=0.626N       |
|COCHRAN-ARMITAGE       |     P=0.036 *                                      |     P=0.270N                                       |
|FISHER EXACT           |                     P=0.309         P=0.056        |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibrosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.3%            0.0%            0.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/36 (3%)       0/33 (0%)       0/25 (0%)      |     0/32 (0%)       0/33 (0%)       0/17 (0%)      |
|FIRST INCIDENCE (DAYS) |      603             ---             ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.107N        P=0.238N        P=0.271N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.085N        P=0.197N        P=0.224N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.097N        P=0.241N        P=0.238N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.095N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.247N        P=0.247N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE  16
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       3/50 (6%)       6/50 (12%)     |     1/50 (2%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      8.0%            9.1%           19.1%          |      3.1%            0.0%            0.0%          |
|TERMINAL (d)           |     2/36 (6%)       3/33 (9%)       2/25 (8%)      |     1/32 (3%)       0/33 (0%)       0/17 (0%)      |
|FIRST INCIDENCE (DAYS) |      603             729 (T)         674           |      729 (T)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.103         P=0.636         P=0.159        |     P=0.337N        P=0.494N        P=0.626N       |
|INCIDENTAL TUMOR       |     P=0.452         P=0.661N        P=0.590N       |     P=0.337N        P=0.494N        P=0.626N       |
|LOGISTIC REGRESSION    |     P=0.173         P=0.647N        P=0.243        |     P=0.337N        P=0.494N        P=0.626N       |
|COCHRAN-ARMITAGE       |     P=0.179                                        |     P=0.270N                                       |
|FISHER EXACT           |                     P=0.661N        P=0.243        |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    38/50 (76%)     41/50 (82%)     42/49 (86%)     |                                                    |
|ADJUSTED (b)           |     92.7%           95.3%           95.3%          |                                                    |
|TERMINAL (d)           |    33/36 (92%)     31/33 (94%)     23/25 (92%)     |                                                    |
|FIRST INCIDENCE (DAYS) |      505             540             458           |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.004 **      P=0.166         P=0.006 **     |                                                    |
|INCIDENTAL TUMOR       |     P=0.212         P=0.508         P=0.276        |                                                    |
|LOGISTIC REGRESSION    |     P=0.292         P=0.615         P=0.332        |                                                    |
|COCHRAN-ARMITAGE       |     P=0.134                                        |                                                    |
|FISHER EXACT           |                     P=0.312         P=0.166        |                                                    |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE  17
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    14/50 (28%)      8/48 (17%)      4/50 (8%)      |     2/50 (4%)       2/50 (4%)       3/50 (6%)      |
|ADJUSTED (b)           |     36.4%           25.0%           14.1%          |      6.3%            6.1%           17.6%          |
|TERMINAL (d)           |    12/36 (33%)      8/32 (25%)      3/25 (12%)     |     2/32 (6%)       2/33 (6%)       3/17 (18%)     |
|FIRST INCIDENCE (DAYS) |      463             729 (T)         630           |      729 (T)         729 (T)         729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.029N*       P=0.166N        P=0.043N*      |     P=0.177         P=0.685N        P=0.226        |
|INCIDENTAL TUMOR       |     P=0.030N*       P=0.181N        P=0.042N*      |     P=0.177         P=0.685N        P=0.226        |
|LOGISTIC REGRESSION    |     P=0.006N**      P=0.108N        P=0.009N**     |     P=0.177         P=0.685N        P=0.226        |
|COCHRAN-ARMITAGE       |     P=0.006N**                                     |     P=0.407                                        |
|FISHER EXACT           |                     P=0.135N        P=0.009N**     |                     P=0.691N        P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/48 (2%)       2/50 (4%)      |     1/50 (2%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |      0.0%            2.2%            8.0%          |      3.1%            3.0%            5.9%          |
|TERMINAL (d)           |     0/36 (0%)       0/32 (0%)       2/25 (8%)      |     1/32 (3%)       1/33 (3%)       1/17 (6%)      |
|FIRST INCIDENCE (DAYS) |      ---             574             729 (T)       |      729 (T)         729 (T)         729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.110         P=0.523         P=0.162        |     P=0.486         P=0.755N        P=0.614        |
|INCIDENTAL TUMOR       |     P=0.125         P=0.567         P=0.162        |     P=0.486         P=0.755N        P=0.614        |
|LOGISTIC REGRESSION    |     P=0.144         P=0.419         P=0.162        |     P=0.486         P=0.755N        P=0.614        |
|COCHRAN-ARMITAGE       |     P=0.144                                        |     P=0.640                                        |
|FISHER EXACT           |                     P=0.490         P=0.247        |                     P=0.753N        P=0.753N       |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE  18
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    14/50 (28%)      9/48 (19%)      6/50 (12%)     |     3/50 (6%)       3/50 (6%)       4/50 (8%)      |
|ADJUSTED (b)           |     36.4%           26.7%           22.0%          |      9.4%            9.1%           23.5%          |
|TERMINAL (d)           |    12/36 (33%)      8/32 (25%)      5/25 (20%)     |     3/32 (9%)       3/33 (9%)       4/17 (24%)     |
|FIRST INCIDENCE (DAYS) |      463             574             630           |      729 (T)         729 (T)         729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.110N        P=0.237N        P=0.147N       |     P=0.150         P=0.650N        P=0.182        |
|INCIDENTAL TUMOR       |     P=0.104N        P=0.246N        P=0.145N       |     P=0.150         P=0.650N        P=0.182        |
|LOGISTIC REGRESSION    |     P=0.028N*       P=0.167N        P=0.038N*      |     P=0.150         P=0.650N        P=0.182        |
|COCHRAN-ARMITAGE       |     P=0.029N*                                      |     P=0.421                                        |
|FISHER EXACT           |                     P=0.200N        P=0.039N*      |                     P=0.661N        P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       2/48 (4%)       3/50 (6%)      |     0/50 (0%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |      2.8%            5.3%           10.6%          |      0.0%            2.7%            5.9%          |
|TERMINAL (d)           |     1/36 (3%)       1/32 (3%)       2/25 (8%)      |     0/32 (0%)       0/33 (0%)       1/17 (6%)      |
|FIRST INCIDENCE (DAYS) |      729 (T)         574             674           |      ---             697             729 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.159         P=0.486         P=0.213        |     P=0.218         P=0.500         P=0.374        |
|INCIDENTAL TUMOR       |     P=0.273         P=0.511         P=0.373        |     P=0.298         P=0.500         P=0.374        |
|LOGISTIC REGRESSION    |     P=0.224         P=0.487         P=0.279        |     P=0.259         P=0.498         P=0.374        |
|COCHRAN-ARMITAGE       |     P=0.224                                        |     P=0.332                                        |
|FISHER EXACT           |                     P=0.485         P=0.309        |                     P=0.500         P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE  19
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/48 (0%)       2/50 (4%)      |     0/50 (0%)       2/50 (4%)       3/50 (6%)      |
|ADJUSTED (b)           |      0.0%            0.0%            7.4%          |      0.0%            6.1%           16.4%          |
|TERMINAL (d)           |     0/36 (0%)       0/32 (0%)       1/25 (4%)      |     0/32 (0%)       2/33 (6%)       2/17 (12%)     |
|FIRST INCIDENCE (DAYS) |      ---             ---             696           |      ---             729 (T)         718           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.068           (e)           P=0.175        |     P=0.021 *       P=0.245         P=0.040 *      |
|INCIDENTAL TUMOR       |     P=0.166           (e)           P=0.427        |     P=0.032 *       P=0.245         P=0.067        |
|LOGISTIC REGRESSION    |     P=0.090           (e)           P=0.224        |     P=0.023 *       P=0.245         P=0.044 *      |
|COCHRAN-ARMITAGE       |     P=0.098                                        |     P=0.082                                        |
|FISHER EXACT           |                       (e)           P=0.247        |                     P=0.247         P=0.121        |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       2/48 (4%)       5/50 (10%)     |     0/50 (0%)       3/50 (6%)       4/50 (8%)      |
|ADJUSTED (b)           |      2.8%            5.3%           17.6%          |      0.0%            8.6%           22.0%          |
|TERMINAL (d)           |     1/36 (3%)       1/32 (3%)       3/25 (12%)     |     0/32 (0%)       2/33 (6%)       3/17 (18%)     |
|FIRST INCIDENCE (DAYS) |      729 (T)         574             674           |      ---             697             718           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.032 *       P=0.486         P=0.052        |     P=0.008 **      P=0.127         P=0.013 *      |
|INCIDENTAL TUMOR       |     P=0.109         P=0.511         P=0.185        |     P=0.017 *       P=0.127         P=0.023 *      |
|LOGISTIC REGRESSION    |     P=0.060         P=0.487         P=0.087        |     P=0.011 *       P=0.120         P=0.014 *      |
|COCHRAN-ARMITAGE       |     P=0.061                                        |     P=0.048 *                                      |
|FISHER EXACT           |                     P=0.485         P=0.102        |                     P=0.121         P=0.059        |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE  20
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |    10/50 (20%)     13/50 (26%)     12/50 (24%)     |
|ADJUSTED (b)           |                                                    |     30.0%           34.7%           40.6%          |
|TERMINAL (d)           |                                                    |     9/32 (28%)      9/33 (27%)      4/17 (24%)     |
|FIRST INCIDENCE (DAYS) |                                                    |      683             617             394           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.050         P=0.345         P=0.073        |
|INCIDENTAL TUMOR       |                                                    |     P=0.310         P=0.340         P=0.321        |
|LOGISTIC REGRESSION    |                                                    |     P=0.249         P=0.311         P=0.321        |
|COCHRAN-ARMITAGE       |                                                    |     P=0.361                                        |
|FISHER EXACT           |                                                    |                     P=0.318         P=0.405        |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     0/50 (0%)       0/50 (0%)       3/50 (6%)      |
|ADJUSTED (b)           |                                                    |      0.0%            0.0%           12.6%          |
|TERMINAL (d)           |                                                    |     0/32 (0%)       0/33 (0%)       1/17 (6%)      |
|FIRST INCIDENCE (DAYS) |                                                    |      ---             ---             604           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.015 *         (e)           P=0.057        |
|INCIDENTAL TUMOR       |                                                    |     P=0.053           (e)           P=0.145        |
|LOGISTIC REGRESSION    |                                                    |     P=0.032 *         (e)           P=0.099        |
|COCHRAN-ARMITAGE       |                                                    |     P=0.038 *                                      |
|FISHER EXACT           |                                                    |                       (e)           P=0.121        |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE  21
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |    10/50 (20%)     13/50 (26%)     15/50 (30%)     |
|ADJUSTED (b)           |                                                    |     30.0%           34.7%           49.2%          |
|TERMINAL (d)           |                                                    |     9/32 (28%)      9/33 (27%)      5/17 (29%)     |
|FIRST INCIDENCE (DAYS) |                                                    |      683             617             394           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.009 **      P=0.345         P=0.014 *      |
|INCIDENTAL TUMOR       |                                                    |     P=0.127         P=0.340         P=0.133        |
|LOGISTIC REGRESSION    |                                                    |     P=0.084         P=0.311         P=0.117        |
|COCHRAN-ARMITAGE       |                                                    |     P=0.150                                        |
|FISHER EXACT           |                                                    |                     P=0.318         P=0.178        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     5/50 (10%)     14/50 (28%)     13/50 (26%)     |    14/50 (28%)     16/50 (32%)     20/50 (40%)     |
|ADJUSTED (b)           |     12.8%           39.6%           37.3%          |     37.4%           38.4%           64.4%          |
|TERMINAL (d)           |     3/36 (8%)      12/33 (36%)      6/25 (24%)     |    10/32 (31%)      8/33 (24%)      7/17 (41%)     |
|FIRST INCIDENCE (DAYS) |      539             620             584           |      335             561             469           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.010 **      P=0.017 *       P=0.018 *      |     P=0.006 **      P=0.441         P=0.006 **     |
|INCIDENTAL TUMOR       |     P=0.060         P=0.024 *       P=0.115        |     P=0.143         P=0.372         P=0.104        |
|LOGISTIC REGRESSION    |     P=0.033 *       P=0.025 *       P=0.035 *      |     P=0.076         P=0.399         P=0.093        |
|COCHRAN-ARMITAGE       |     P=0.033 *                                      |     P=0.122                                        |
|FISHER EXACT           |                     P=0.020 *       P=0.033 *      |                     P=0.414         P=0.146        |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE  22
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma Benign, Malignant, NOS                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       4/50 (8%)       4/50 (8%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      2.3%           10.5%           13.8%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/36 (0%)       2/33 (6%)       2/25 (8%)      |     0/32 (0%)       0/33 (0%)       0/17 (0%)      |
|FIRST INCIDENCE (DAYS) |      505             603             676           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.105         P=0.190         P=0.133        |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.245         P=0.180         P=0.339        |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.144         P=0.148         P=0.177        |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.146                                        |       (e)                                          |
|FISHER EXACT           |                     P=0.181         P=0.181        |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Osteosarcoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       2/50 (4%)       0/50 (0%)      |     0/50 (0%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |      0.0%            5.0%            0.0%          |      0.0%            2.5%            2.3%          |
|TERMINAL (d)           |     0/36 (0%)       0/33 (0%)       0/25 (0%)      |     0/32 (0%)       0/33 (0%)       0/17 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             540             ---           |      ---             652             492           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.644         P=0.248           (e)          |     P=0.290         P=0.505         P=0.500        |
|INCIDENTAL TUMOR       |     P=0.517N        P=0.362           (e)          |     P=0.529         P=0.500         P=0.718        |
|LOGISTIC REGRESSION    |     P=0.640         P=0.202           (e)          |     P=0.354         P=0.502         P=0.538        |
|COCHRAN-ARMITAGE       |     P=0.667                                        |     P=0.332                                        |
|FISHER EXACT           |                     P=0.247           (e)          |                     P=0.500         P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE  23
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Osteosarcoma or Osteoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       2/50 (4%)       0/50 (0%)      |     0/50 (0%)       1/50 (2%)       1/50 (2%)      |
|ADJUSTED (b)           |      0.0%            5.0%            0.0%          |      0.0%            2.5%            2.3%          |
|TERMINAL (d)           |     0/36 (0%)       0/33 (0%)       0/25 (0%)      |     0/32 (0%)       0/33 (0%)       0/17 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             540             ---           |      ---             652             492           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.644         P=0.248           (e)          |     P=0.290         P=0.505         P=0.500        |
|INCIDENTAL TUMOR       |     P=0.517N        P=0.362           (e)          |     P=0.529         P=0.500         P=0.718        |
|LOGISTIC REGRESSION    |     P=0.640         P=0.202           (e)          |     P=0.354         P=0.502         P=0.538        |
|COCHRAN-ARMITAGE       |     P=0.667                                        |     P=0.332                                        |
|FISHER EXACT           |                     P=0.247           (e)          |                     P=0.500         P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    46/50 (92%)     46/50 (92%)     49/50 (98%)     |    35/50 (70%)     38/50 (76%)     32/50 (64%)     |
|ADJUSTED (b)           |    100.0%          100.0%          100.0%          |     89.7%           90.4%           93.8%          |
|TERMINAL (d)           |    36/36 (100%)    33/33 (100%)    25/25 (100%)    |    28/32 (88%)     29/33 (88%)     15/17 (88%)     |
|FIRST INCIDENCE (DAYS) |      403             506             458           |      619             588             394           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.008 **      P=0.404         P=0.013 *      |     P=0.003 **      P=0.410         P=0.005 **     |
|INCIDENTAL TUMOR       |     P=0.445         P=0.286N        P=0.582        |     P=0.262         P=0.377         P=0.270        |
|LOGISTIC REGRESSION    |     P=0.576         P=0.125N        P=0.769        |     P=0.248         P=0.289         P=0.295        |
|COCHRAN-ARMITAGE       |     P=0.147                                        |     P=0.294N                                       |
|FISHER EXACT           |                     P=0.643N        P=0.181        |                     P=0.326         P=0.335N       |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE  24
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         44MG/KG         88 MG/KG      |      CONTROL         44MG/KG         88 MG/KG      |
|                       |      MALE            LOW MALE        HIGHMALE      |      FEMALE          LOW FEM         HIGHFEM       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    16/50 (32%)     29/50 (58%)     31/50 (62%)     |    26/50 (52%)     25/50 (50%)     30/50 (60%)     |
|ADJUSTED (b)           |     36.6%           65.4%           74.4%          |     59.2%           54.2%           82.2%          |
|TERMINAL (d)           |     9/36 (25%)     18/33 (55%)     15/25 (60%)     |    15/32 (47%)     12/33 (36%)     11/17 (65%)     |
|FIRST INCIDENCE (DAYS) |      350             441             528           |      335              85             469           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P=0.016 *       P=0.001 **     |     P=0.010 **      P=0.478N        P=0.008 **     |
|INCIDENTAL TUMOR       |     P=0.007 **      P=0.014 *       P=0.009 **     |     P=0.460         P=0.514         P=0.383        |
|LOGISTIC REGRESSION    |     P=0.002 **      P=0.006 **      P=0.002 **     |     P=0.390         P=0.493         P=0.216        |
|COCHRAN-ARMITAGE       |     P=0.002 **                                     |     P=0.242                                        |
|FISHER EXACT           |                     P=0.008 **      P=0.002 **     |                     P=0.500N        P=0.273        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    48/50 (96%)     48/50 (96%)     49/50 (98%)     |    45/50 (90%)     46/50 (92%)     44/50 (88%)     |
|ADJUSTED (b)           |    100.0%          100.0%          100.0%          |     95.7%           97.9%          100.0%          |
|TERMINAL (d)           |    36/36 (100%)    33/33 (100%)    25/25 (100%)    |    30/32 (94%)     32/33 (97%)     17/17 (100%)    |
|FIRST INCIDENCE (DAYS) |      350             441             458           |      335              85             394           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.025 *       P=0.419         P=0.035 *      |     P=0.001 **      P=0.562         P=0.002 **     |
|INCIDENTAL TUMOR       |     P=0.493         P=0.668N        P=0.751        |     P=0.558N        P=0.297         P=0.615N       |
|LOGISTIC REGRESSION    |     P=0.557N        P=0.458N        P=0.661N       |     P=0.557         P=0.308         P=0.587        |
|COCHRAN-ARMITAGE       |     P=0.391                                        |     P=0.435N                                       |
|FISHER EXACT           |                     P=0.691N        P=0.500        |                     P=0.500         P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/05/94                     EXPERIMENT: 05042 TEST: 01                                                 PAGE  25
                      STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- TRIS 2-CHLOROETHYL PHOSPHATE
 
                                                 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).

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