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TDMS Study 05134-02 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Northwest                                 1,3 BUTADIENE (BUTADIENE)                              DATE: 09/21/94       
EXPERIMENT: 05134 TEST: 02                                                                                     TIME: 14:24:25       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01ES5510500          ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                                             NTP C#: 50602C       
PATHOLOGIST: R. MILLER                                                                                         CAS: 106-99-0        
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                          LOW DOSE GROUPS                                                           
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE 001    CONTROL                                                                       
                                       INCLUDE 002    CONTROL                                                                       
                                       INCLUDE 003    6.25 PPM                                                                      
                                       INCLUDE 004    6.25 PPM                                                                      
                                       INCLUDE 005    20 PPM                                                                        
                                       INCLUDE 006    20 PPM                                                                        
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: Battelle Northwest                                 1,3 BUTADIENE (BUTADIENE)                              DATE: 09/21/94      
EXPERIMENT: 05134 TEST: 02                                                                                     TIME: 14:24:25      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01ES5510500          ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                                             NTP C#: 50602C      
PATHOLOGIST: R. MILLER                                                                                         CAS: 106-99-0       
 
 
 
 
 
                                                    MICE(B6C3F1)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Gland
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Gallbladder
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Larynx
                                                    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: Battelle Northwest                                 1,3 BUTADIENE (BUTADIENE)                              DATE: 09/21/94       
EXPERIMENT: 05134 TEST: 02                                                                                     TIME: 14:24:25       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01ES5510500          ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                                             NTP C#: 50602C       
PATHOLOGIST: R. MILLER                                                                                         CAS: 106-99-0        
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                   IN THE ANALYSIS OF THE STUDY OF 1,3 BUTADIENE (BUTADIENE)
 
              ====================================================================================================
 
                                                           MALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Harderian Gland               Carcinoma or Adenoma
                             Liver                         Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Lung                          Alveolar/Bronchiolar Carcinoma
                             All Organs                    Histiocytic Sarcoma
                                                           Malignant Lymphoma And Histiocytic Sarcoma
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
                                                           FEMALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Lung                          Alveolar/Bronchiolar Adenoma
                                                           Alveolar/Bronchiolar Carcinoma
                                                           Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
                             Stomach, Forestomach          Squamous Cell Carcinoma or Papilloma Squamous
                                                           Squamous Cell Papilloma
                             Uterus                        Polyp Stromal
                             All Organs                    Histiocytic Sarcoma
                                                           Malignant Lymphoma And Histiocytic Sarcoma
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   1
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         6.25 PPM        20 PPM        |      CONTROL         6.25 PPM        20 PPM        |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/70 (3%)       4/69 (6%)       0/70 (0%)      |     1/70 (1%)       0/69 (0%)       0/68 (0%)      |
|ADJUSTED (b)           |      5.1%           10.3%            0.0%          |      2.7%            0.0%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     1/35 (3%)       4/39 (10%)      0/24 (0%)      |     1/37 (3%)       0/33 (0%)       0/24 (0%)      |
|FIRST INCIDENCE (DAYS) |      596             734 (T)         ---           |      734 (T)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.238N        P=0.387         P=0.296N       |     P=0.479N        P=0.523N        P=0.586N       |
|INCIDENTAL TUMOR       |     P=0.183N        P=0.380         P=0.187N       |     P=0.479N        P=0.523N        P=0.586N       |
|LOGISTIC REGRESSION    |     P=0.195N        P=0.363         P=0.256N       |     P=0.479N        P=0.523N        P=0.586N       |
|COCHRAN-ARMITAGE       |     P=0.153N                                       |     P=0.415N                                       |
|FISHER EXACT           |                     P=0.333         P=0.248N       |                     P=0.504N        P=0.507N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/70 (0%)       1/68 (1%)       0/67 (0%)      |     0/70 (0%)       0/68 (0%)       2/67 (3%)      |
|ADJUSTED (b)           |      0.0%            2.6%            0.0%          |      0.0%            0.0%            6.8%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     0/35 (0%)       1/39 (3%)       0/24 (0%)      |     0/37 (0%)       0/33 (0%)       1/24 (4%)      |
|FIRST INCIDENCE (DAYS) |      ---             734 (T)         ---           |      ---             ---             645           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.773N        P=0.522           (e)          |     P=0.062           (e)           P=0.178        |
|INCIDENTAL TUMOR       |     P=0.773N        P=0.522           (e)          |     P=0.102           (e)           P=0.251        |
|LOGISTIC REGRESSION    |     P=0.773N        P=0.522           (e)          |     P=0.069           (e)           P=0.193        |
|COCHRAN-ARMITAGE       |     P=0.706N                                       |     P=0.088                                        |
|FISHER EXACT           |                     P=0.493           (e)          |                       (e)           P=0.237        |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   2
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         6.25 PPM        20 PPM        |      CONTROL         6.25 PPM        20 PPM        |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/70 (9%)       7/70 (10%)     10/70 (14%)     |    10/70 (14%)     11/70 (16%)      7/70 (10%)     |
|ADJUSTED (b)           |     14.8%           17.3%           28.3%          |     23.5%           30.4%           22.1%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       2/10 (20%)     |     2/10 (20%)      1/10 (10%)      1/10 (10%)     |
|TERMINAL (d)           |     2/35 (6%)       6/39 (15%)      4/24 (17%)     |     7/37 (19%)      9/33 (27%)      4/24 (17%)     |
|FIRST INCIDENCE (DAYS) |      543             652             456 (I)       |      457 (I)         457 (I)         457 (I)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.055         P=0.575         P=0.107        |     P=0.531N        P=0.409         P=0.565N       |
|INCIDENTAL TUMOR       |     P=0.211         P=0.492         P=0.297        |     P=0.437N        P=0.439         P=0.497N       |
|LOGISTIC REGRESSION    |     P=0.121         P=0.548         P=0.178        |     P=0.342N        P=0.473         P=0.386N       |
|COCHRAN-ARMITAGE       |     P=0.173                                        |     P=0.238N                                       |
|FISHER EXACT           |                     P=0.500         P=0.213        |                     P=0.500         P=0.303N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/70 (9%)       7/70 (10%)     11/70 (16%)     |    10/70 (14%)     11/70 (16%)      8/70 (11%)     |
|ADJUSTED (b)           |     14.8%           17.3%           31.9%          |     23.5%           30.4%           23.8%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       2/10 (20%)     |     2/10 (20%)      1/10 (10%)      1/10 (10%)     |
|TERMINAL (d)           |     2/35 (6%)       6/39 (15%)      5/24 (21%)     |     7/37 (19%)      9/33 (27%)      4/24 (17%)     |
|FIRST INCIDENCE (DAYS) |      543             652             456 (I)       |      457 (I)         457 (I)         457 (I)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.028 *       P=0.575         P=0.065        |     P=0.492         P=0.409         P=0.534        |
|INCIDENTAL TUMOR       |     P=0.131         P=0.492         P=0.203        |     P=0.524N        P=0.439         P=0.556N       |
|LOGISTIC REGRESSION    |     P=0.070         P=0.548         P=0.118        |     P=0.446N        P=0.473         P=0.484N       |
|COCHRAN-ARMITAGE       |     P=0.112                                        |     P=0.332N                                       |
|FISHER EXACT           |                     P=0.500         P=0.150        |                     P=0.500         P=0.401N       |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   3
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         6.25 PPM        20 PPM        |      CONTROL         6.25 PPM        20 PPM        |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/70 (0%)       1/70 (1%)       1/70 (1%)      |     0/70 (0%)       3/70 (4%)       0/70 (0%)      |
|ADJUSTED (b)           |      0.0%            2.6%            3.8%          |      0.0%            9.1%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     0/35 (0%)       1/39 (3%)       0/24 (0%)      |     0/37 (0%)       3/33 (9%)       0/24 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             734 (T)         689           |      ---             734 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.339         P=0.522         P=0.430        |     P=0.608N        P=0.101           (e)          |
|INCIDENTAL TUMOR       |     P=0.470         P=0.522         P=0.617        |     P=0.608N        P=0.101           (e)          |
|LOGISTIC REGRESSION    |     P=0.384         P=0.522         P=0.473        |     P=0.608N        P=0.101           (e)          |
|COCHRAN-ARMITAGE       |     P=0.437                                        |     P=0.483N                                       |
|FISHER EXACT           |                     P=0.500         P=0.500        |                     P=0.122           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/70 (0%)       2/70 (3%)       0/70 (0%)      |     1/69 (1%)       0/69 (0%)       0/70 (0%)      |
|ADJUSTED (b)           |      0.0%            5.0%            0.0%          |      2.7%            0.0%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     0/35 (0%)       1/39 (3%)       0/24 (0%)      |     1/37 (3%)       0/33 (0%)       0/24 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             723             ---           |      734 (T)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.665N        P=0.267           (e)          |     P=0.479N        P=0.523N        P=0.586N       |
|INCIDENTAL TUMOR       |     P=0.530N        P=0.252           (e)          |     P=0.479N        P=0.523N        P=0.586N       |
|LOGISTIC REGRESSION    |     P=0.645N        P=0.260           (e)          |     P=0.479N        P=0.523N        P=0.586N       |
|COCHRAN-ARMITAGE       |     P=0.563N                                       |     P=0.409N                                       |
|FISHER EXACT           |                     P=0.248           (e)          |                     P=0.500N        P=0.496N       |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   4
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         6.25 PPM        20 PPM        |      CONTROL         6.25 PPM        20 PPM        |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    19/70 (27%)     13/70 (19%)     24/70 (34%)     |    12/69 (17%)     11/69 (16%)      9/70 (13%)     |
|ADJUSTED (b)           |     37.9%           31.3%           56.0%          |     30.9%           29.2%           30.1%          |
|INTERIM SACRIFICE 1 (c)|     4/10 (40%)      0/10 (0%)       1/10 (10%)     |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     2/10 (20%)      0/10 (0%)       4/10 (40%)     |     1/10 (10%)      1/10 (10%)      0/10 (0%)      |
|TERMINAL (d)           |     9/35 (26%)     11/39 (28%)      8/24 (33%)     |    11/37 (30%)      8/33 (24%)      6/24 (25%)     |
|FIRST INCIDENCE (DAYS) |      281 (I)         484             281 (I)       |      457 (I)         457 (I)         365           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.019 *       P=0.111N        P=0.081        |     P=0.491         P=0.586         P=0.522        |
|INCIDENTAL TUMOR       |     P=0.107         P=0.177N        P=0.251        |     P=0.417N        P=0.557N        P=0.515N       |
|LOGISTIC REGRESSION    |     P=0.096         P=0.149N        P=0.226        |     P=0.428N        P=0.523N        P=0.468N       |
|COCHRAN-ARMITAGE       |     P=0.115                                        |     P=0.274N                                       |
|FISHER EXACT           |                     P=0.157N        P=0.232        |                     P=0.500N        P=0.306N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    11/70 (16%)     17/70 (24%)     16/70 (23%)     |     4/69 (6%)       6/69 (9%)       8/70 (11%)     |
|ADJUSTED (b)           |     26.0%           37.7%           44.8%          |     10.3%           14.5%           25.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       1/10 (10%)      0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     5/35 (14%)     12/39 (31%)      7/24 (29%)     |     3/37 (8%)       2/33 (6%)       3/24 (13%)     |
|FIRST INCIDENCE (DAYS) |      540             456 (I)         517           |      677             467             600           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.057         P=0.228         P=0.071        |     P=0.056         P=0.330         P=0.064        |
|INCIDENTAL TUMOR       |     P=0.358         P=0.128         P=0.335        |     P=0.239         P=0.413         P=0.226        |
|LOGISTIC REGRESSION    |     P=0.438         P=0.106         P=0.412        |     P=0.298         P=0.400         P=0.104        |
|COCHRAN-ARMITAGE       |     P=0.243                                        |     P=0.172                                        |
|FISHER EXACT           |                     P=0.145         P=0.196        |                     P=0.372         P=0.190        |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   5
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         6.25 PPM        20 PPM        |      CONTROL         6.25 PPM        20 PPM        |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    27/70 (39%)     24/70 (34%)     35/70 (50%)     |    16/69 (23%)     15/69 (22%)     15/70 (21%)     |
|ADJUSTED (b)           |     52.4%           53.8%           72.5%          |     40.3%           35.6%           45.3%          |
|INTERIM SACRIFICE 1 (c)|     4/10 (40%)      0/10 (0%)       1/10 (10%)     |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     2/10 (20%)      1/10 (10%)      4/10 (40%)     |     1/10 (10%)      1/10 (10%)      0/10 (0%)      |
|TERMINAL (d)           |    13/35 (37%)     19/39 (49%)     12/24 (50%)     |    14/37 (38%)      8/33 (24%)      8/24 (33%)     |
|FIRST INCIDENCE (DAYS) |      281 (I)         456 (I)         281 (I)       |      457 (I)         457 (I)         365           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.005 **      P=0.246N        P=0.027 *      |     P=0.212         P=0.553         P=0.226        |
|INCIDENTAL TUMOR       |     P=0.083         P=0.377N        P=0.186        |     P=0.506N        P=0.514N        P=0.557        |
|LOGISTIC REGRESSION    |     P=0.038 *       P=0.324N        P=0.095        |     P=0.448         P=0.523N        P=0.454        |
|COCHRAN-ARMITAGE       |     P=0.064                                        |     P=0.465N                                       |
|FISHER EXACT           |                     P=0.363N        P=0.117        |                     P=0.500N        P=0.482N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    27/70 (39%)     24/70 (34%)     35/70 (50%)     |    16/69 (23%)     15/69 (22%)     15/70 (21%)     |
|ADJUSTED (b)           |     52.4%           53.8%           72.5%          |     40.3%           35.6%           45.3%          |
|INTERIM SACRIFICE 1 (c)|     4/10 (40%)      0/10 (0%)       1/10 (10%)     |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     2/10 (20%)      1/10 (10%)      4/10 (40%)     |     1/10 (10%)      1/10 (10%)      0/10 (0%)      |
|TERMINAL (d)           |    13/35 (37%)     19/39 (49%)     12/24 (50%)     |    14/37 (38%)      8/33 (24%)      8/24 (33%)     |
|FIRST INCIDENCE (DAYS) |      281 (I)         456 (I)         281 (I)       |      457 (I)         457 (I)         365           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.005 **      P=0.246N        P=0.027 *      |     P=0.212         P=0.553         P=0.226        |
|INCIDENTAL TUMOR       |     P=0.083         P=0.377N        P=0.186        |     P=0.506N        P=0.514N        P=0.557        |
|LOGISTIC REGRESSION    |     P=0.038 *       P=0.324N        P=0.095        |     P=0.448         P=0.523N        P=0.454        |
|COCHRAN-ARMITAGE       |     P=0.064                                        |     P=0.465N                                       |
|FISHER EXACT           |                     P=0.363N        P=0.117        |                     P=0.500N        P=0.482N       |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   6
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         6.25 PPM        20 PPM        |      CONTROL         6.25 PPM        20 PPM        |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    18/70 (26%)     21/70 (30%)     11/70 (16%)     |     4/70 (6%)      11/70 (16%)     12/70 (17%)     |
|ADJUSTED (b)           |     46.9%           48.1%           29.3%          |     10.5%           30.9%           40.7%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       1/10 (10%)      1/10 (10%)     |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |    15/35 (43%)     17/39 (44%)      3/24 (13%)     |     3/37 (8%)       9/33 (27%)      8/24 (33%)     |
|FIRST INCIDENCE (DAYS) |      572             281 (I)         281 (I)       |      714             524             492           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.312N        P=0.502         P=0.346N       |     P=0.004 **      P=0.031 *       P=0.003 **     |
|INCIDENTAL TUMOR       |     P=0.081N        P=0.478         P=0.108N       |     P=0.020 *       P=0.045 *       P=0.015 *      |
|LOGISTIC REGRESSION    |     P=0.111N        P=0.446         P=0.159N       |     P=0.012 *       P=0.038 *       P=0.009 **     |
|COCHRAN-ARMITAGE       |     P=0.062N                                       |     P=0.053                                        |
|FISHER EXACT           |                     P=0.353         P=0.105N       |                     P=0.049 *       P=0.030 *      |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/70 (9%)       6/70 (9%)      11/70 (16%)     |     0/70 (0%)       5/70 (7%)      11/70 (16%)     |
|ADJUSTED (b)           |     15.5%           15.4%           38.3%          |      0.0%           13.3%           42.9%          |
|INTERIM SACRIFICE 1 (c)|     1/10 (10%)      0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     5/35 (14%)      6/39 (15%)      7/24 (29%)     |     0/37 (0%)       3/33 (9%)      10/24 (42%)     |
|FIRST INCIDENCE (DAYS) |      281 (I)         734 (T)         568           |      ---             519             507           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.012 *       P=0.550N        P=0.038 *      |     P<0.001 **      P=0.029 *       P<0.001 **     |
|INCIDENTAL TUMOR       |     P=0.035 *       P=0.550N        P=0.088        |     P<0.001 **      P=0.045 *       P<0.001 **     |
|LOGISTIC REGRESSION    |     P=0.039 *       P=0.577N        P=0.086        |     P<0.001 **      P=0.032 *       P<0.001 **     |
|COCHRAN-ARMITAGE       |     P=0.096                                        |     P<0.001 **                                     |
|FISHER EXACT           |                     P=0.618N        P=0.150        |                     P=0.029 *       P<0.001 **     |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   7
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         6.25 PPM        20 PPM        |      CONTROL         6.25 PPM        20 PPM        |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    22/70 (31%)     24/70 (34%)     20/70 (29%)     |     4/70 (6%)      15/70 (21%)     19/70 (27%)     |
|ADJUSTED (b)           |     55.5%           55.2%           54.3%          |     10.5%           39.5%           63.7%          |
|INTERIM SACRIFICE 1 (c)|     1/10 (10%)      1/10 (10%)      1/10 (10%)     |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |    18/35 (51%)     20/39 (51%)      9/24 (38%)     |     3/37 (8%)      11/33 (33%)     14/24 (58%)     |
|FIRST INCIDENCE (DAYS) |      281 (I)         281 (I)         281 (I)       |      714             519             492           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.218         P=0.551N        P=0.282        |     P<0.001 **      P=0.004 **      P<0.001 **     |
|INCIDENTAL TUMOR       |     P=0.508N        P=0.575N        P=0.512N       |     P<0.001 **      P=0.006 **      P<0.001 **     |
|LOGISTIC REGRESSION    |     P=0.548N        P=0.534         P=0.579N       |     P<0.001 **      P=0.004 **      P<0.001 **     |
|COCHRAN-ARMITAGE       |     P=0.357N                                       |     P=0.002 **                                     |
|FISHER EXACT           |                     P=0.429         P=0.427N       |                     P=0.006 **      P<0.001 **     |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Adenoacanthoma                                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/70 (0%)       0/70 (0%)       0/70 (0%)      |     0/70 (0%)       1/70 (1%)       2/70 (3%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      0.0%            2.9%            7.7%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     0/35 (0%)       0/39 (0%)       0/24 (0%)      |     0/37 (0%)       0/33 (0%)       1/24 (4%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      ---             732             686           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.100         P=0.489         P=0.152        |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.261         P=0.557         P=0.266        |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.123         P=0.491         P=0.184        |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.180                                        |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.500         P=0.248        |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   8
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         6.25 PPM        20 PPM        |      CONTROL         6.25 PPM        20 PPM        |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/70 (0%)       0/70 (0%)       0/70 (0%)      |     0/70 (0%)       2/70 (3%)       2/70 (3%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      0.0%            5.8%            5.7%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     0/35 (0%)       0/39 (0%)       0/24 (0%)      |     0/37 (0%)       1/33 (3%)       0/24 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      ---             732             645           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.173         P=0.221         P=0.192        |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.405         P=0.258         P=0.418        |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.210         P=0.227         P=0.218        |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.260                                        |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.248         P=0.248        |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     2/69 (3%)       4/69 (6%)       1/68 (1%)      |
|ADJUSTED (b)           |                                                    |      5.6%           12.1%            4.2%          |
|INTERIM SACRIFICE 1 (c)|                                                    |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|                                                    |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |                                                    |     2/36 (6%)       4/33 (12%)      1/24 (4%)      |
|FIRST INCIDENCE (DAYS) |                                                    |      734 (T)         734 (T)         734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.504N        P=0.296         P=0.640N       |
|INCIDENTAL TUMOR       |                                                    |     P=0.504N        P=0.296         P=0.640N       |
|LOGISTIC REGRESSION    |                                                    |     P=0.504N        P=0.296         P=0.640N       |
|COCHRAN-ARMITAGE       |                                                    |     P=0.339N                                       |
|FISHER EXACT           |                                                    |                     P=0.340         P=0.506N       |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   9
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         6.25 PPM        20 PPM        |      CONTROL         6.25 PPM        20 PPM        |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/70 (1%)       0/67 (0%)       0/67 (0%)      |     7/70 (10%)     12/69 (17%)      5/68 (7%)      |
|ADJUSTED (b)           |      2.9%            0.0%            0.0%          |     17.4%           33.7%           17.5%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     1/35 (3%)       0/38 (0%)       0/24 (0%)      |     5/37 (14%)     10/33 (30%)      3/24 (13%)     |
|FIRST INCIDENCE (DAYS) |      734 (T)         ---             ---           |      625             653             645           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.473N        P=0.484N        P=0.575N       |     P=0.534N        P=0.107         P=0.600        |
|INCIDENTAL TUMOR       |     P=0.473N        P=0.484N        P=0.575N       |     P=0.348N        P=0.124         P=0.481N       |
|LOGISTIC REGRESSION    |     P=0.473N        P=0.484N        P=0.575N       |     P=0.429N        P=0.132         P=0.552N       |
|COCHRAN-ARMITAGE       |     P=0.417N                                       |     P=0.251N                                       |
|FISHER EXACT           |                     P=0.511N        P=0.511N       |                     P=0.154         P=0.403N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/70 (0%)       1/70 (1%)       1/70 (1%)      |     1/70 (1%)       2/70 (3%)       2/70 (3%)      |
|ADJUSTED (b)           |      0.0%            2.6%            2.5%          |      2.7%            5.2%            8.3%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     0/35 (0%)       1/39 (3%)       0/24 (0%)      |     1/37 (3%)       1/33 (3%)       2/24 (8%)      |
|FIRST INCIDENCE (DAYS) |      ---             734 (T)         585           |      734 (T)         572             734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.374         P=0.522         P=0.486        |     P=0.323         P=0.471         P=0.350        |
|INCIDENTAL TUMOR       |     P=0.502         P=0.522         P=0.662        |     P=0.337         P=0.448         P=0.350        |
|LOGISTIC REGRESSION    |     P=0.416         P=0.522         P=0.500        |     P=0.383         P=0.492         P=0.350        |
|COCHRAN-ARMITAGE       |     P=0.437                                        |     P=0.460                                        |
|FISHER EXACT           |                     P=0.500         P=0.500        |                     P=0.500         P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  10
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         6.25 PPM        20 PPM        |      CONTROL         6.25 PPM        20 PPM        |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/70 (1%)       0/70 (0%)       1/70 (1%)      |     1/70 (1%)       2/70 (3%)       3/70 (4%)      |
|ADJUSTED (b)           |      2.3%            0.0%            3.3%          |      2.4%            5.3%            8.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     0/35 (0%)       0/39 (0%)       0/24 (0%)      |     0/37 (0%)       1/33 (3%)       0/24 (0%)      |
|FIRST INCIDENCE (DAYS) |      572             ---             680           |      677             642             569           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.612         P=0.483N        P=0.729        |     P=0.182         P=0.476         P=0.238        |
|INCIDENTAL TUMOR       |     P=0.618N        P=0.500N        P=0.598N       |     P=0.382         P=0.494         P=0.523        |
|LOGISTIC REGRESSION    |     P=0.639         P=0.503N        P=0.755        |     P=0.544         P=0.491         P=0.282        |
|COCHRAN-ARMITAGE       |     P=0.645                                        |     P=0.258                                        |
|FISHER EXACT           |                     P=0.500N        P=0.752N       |                     P=0.500         P=0.310        |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/70 (1%)       0/70 (0%)       1/70 (1%)      |     1/70 (1%)       2/70 (3%)       3/70 (4%)      |
|ADJUSTED (b)           |      2.3%            0.0%            3.3%          |      2.4%            5.3%            8.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     0/35 (0%)       0/39 (0%)       0/24 (0%)      |     0/37 (0%)       1/33 (3%)       0/24 (0%)      |
|FIRST INCIDENCE (DAYS) |      572             ---             680           |      677             642             569           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.612         P=0.483N        P=0.729        |     P=0.182         P=0.476         P=0.238        |
|INCIDENTAL TUMOR       |     P=0.618N        P=0.500N        P=0.598N       |     P=0.382         P=0.494         P=0.523        |
|LOGISTIC REGRESSION    |     P=0.639         P=0.503N        P=0.755        |     P=0.544         P=0.491         P=0.282        |
|COCHRAN-ARMITAGE       |     P=0.645                                        |     P=0.258                                        |
|FISHER EXACT           |                     P=0.500N        P=0.752N       |                     P=0.500         P=0.310        |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  11
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         6.25 PPM        20 PPM        |      CONTROL         6.25 PPM        20 PPM        |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Sarcoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/70 (1%)       0/70 (0%)       1/70 (1%)      |     1/70 (1%)       2/70 (3%)       2/70 (3%)      |
|ADJUSTED (b)           |      2.3%            0.0%            3.3%          |      2.4%            5.3%            5.7%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     0/35 (0%)       0/39 (0%)       0/24 (0%)      |     0/37 (0%)       1/33 (3%)       0/24 (0%)      |
|FIRST INCIDENCE (DAYS) |      572             ---             680           |      677             642             650           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.612         P=0.483N        P=0.729        |     P=0.359         P=0.476         P=0.415        |
|INCIDENTAL TUMOR       |     P=0.618N        P=0.500N        P=0.598N       |     P=0.608         P=0.494         P=0.722N       |
|LOGISTIC REGRESSION    |     P=0.639         P=0.503N        P=0.755        |     P=0.414         P=0.491         P=0.464        |
|COCHRAN-ARMITAGE       |     P=0.645                                        |     P=0.460                                        |
|FISHER EXACT           |                     P=0.500N        P=0.752N       |                     P=0.500         P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/70 (0%)       1/70 (1%)       1/70 (1%)      |     2/69 (3%)       1/69 (1%)       0/68 (0%)      |
|ADJUSTED (b)           |      0.0%            2.1%            4.2%          |      5.4%            3.0%            0.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     0/35 (0%)       0/39 (0%)       1/24 (4%)      |     2/37 (5%)       1/33 (3%)       0/24 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             587             734 (T)       |      734 (T)         734 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.367         P=0.522         P=0.425        |     P=0.259N        P=0.540N        P=0.338N       |
|INCIDENTAL TUMOR       |     P=0.502         P=0.500         P=0.425        |     P=0.259N        P=0.540N        P=0.338N       |
|LOGISTIC REGRESSION    |     P=0.416         P=0.498         P=0.425        |     P=0.259N        P=0.540N        P=0.338N       |
|COCHRAN-ARMITAGE       |     P=0.437                                        |     P=0.183N                                       |
|FISHER EXACT           |                     P=0.500         P=0.500        |                     P=0.500N        P=0.252N       |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  12
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         6.25 PPM        20 PPM        |      CONTROL         6.25 PPM        20 PPM        |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/70 (1%)       0/70 (0%)       0/70 (0%)      |     0/70 (0%)       0/70 (0%)       3/70 (4%)      |
|ADJUSTED (b)           |      2.5%            0.0%            0.0%          |      0.0%            0.0%           12.5%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     0/35 (0%)       0/39 (0%)       0/24 (0%)      |     0/37 (0%)       0/33 (0%)       3/24 (13%)     |
|FIRST INCIDENCE (DAYS) |      652             ---             ---           |      ---             ---             734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.449N        P=0.481N        P=0.545N       |     P=0.011 *         (e)           P=0.056        |
|INCIDENTAL TUMOR       |     P=0.313N        P=0.500N        P=0.383N       |     P=0.011 *         (e)           P=0.056        |
|LOGISTIC REGRESSION    |     P=0.421N        P=0.495N        P=0.514N       |     P=0.011 *         (e)           P=0.056        |
|COCHRAN-ARMITAGE       |     P=0.411N                                       |     P=0.031 *                                      |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                       (e)           P=0.122        |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/70 (1%)       0/70 (0%)       0/70 (0%)      |     0/70 (0%)       0/70 (0%)       2/70 (3%)      |
|ADJUSTED (b)           |      2.5%            0.0%            0.0%          |      0.0%            0.0%            8.3%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     0/35 (0%)       0/39 (0%)       0/24 (0%)      |     0/37 (0%)       0/33 (0%)       2/24 (8%)      |
|FIRST INCIDENCE (DAYS) |      652             ---             ---           |      ---             ---             734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.449N        P=0.481N        P=0.545N       |     P=0.048 *         (e)           P=0.149        |
|INCIDENTAL TUMOR       |     P=0.313N        P=0.500N        P=0.383N       |     P=0.048 *         (e)           P=0.149        |
|LOGISTIC REGRESSION    |     P=0.421N        P=0.495N        P=0.514N       |     P=0.048 *         (e)           P=0.149        |
|COCHRAN-ARMITAGE       |     P=0.411N                                       |     P=0.092                                        |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                       (e)           P=0.248        |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  13
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         6.25 PPM        20 PPM        |      CONTROL         6.25 PPM        20 PPM        |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/70 (3%)       4/70 (6%)       0/70 (0%)      |     1/70 (1%)       1/69 (1%)       1/69 (1%)      |
|ADJUSTED (b)           |      5.7%            9.8%            0.0%          |      2.4%            2.5%            3.1%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     2/35 (6%)       3/39 (8%)       0/24 (0%)      |     0/37 (0%)       0/33 (0%)       0/24 (0%)      |
|FIRST INCIDENCE (DAYS) |      734 (T)         653             ---           |      677             673             657           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.242N        P=0.388         P=0.324N       |     P=0.604         P=0.747         P=0.689        |
|INCIDENTAL TUMOR       |     P=0.197N        P=0.380         P=0.324N       |     P=0.490N        P=0.702N        P=0.602N       |
|LOGISTIC REGRESSION    |     P=0.206N        P=0.379         P=0.324N       |     P=0.652         P=0.757         P=0.734        |
|COCHRAN-ARMITAGE       |     P=0.153N                                       |     P=0.681                                        |
|FISHER EXACT           |                     P=0.340         P=0.248N       |                     P=0.748         P=0.748        |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/70 (3%)       4/70 (6%)       0/70 (0%)      |     1/70 (1%)       2/69 (3%)       1/69 (1%)      |
|ADJUSTED (b)           |      5.7%            9.8%            0.0%          |      2.4%            5.5%            3.1%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     2/35 (6%)       3/39 (8%)       0/24 (0%)      |     0/37 (0%)       1/33 (3%)       0/24 (0%)      |
|FIRST INCIDENCE (DAYS) |      734 (T)         653             ---           |      677             673             657           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.242N        P=0.388         P=0.324N       |     P=0.616         P=0.473         P=0.689        |
|INCIDENTAL TUMOR       |     P=0.197N        P=0.380         P=0.324N       |     P=0.466N        P=0.554         P=0.602N       |
|LOGISTIC REGRESSION    |     P=0.206N        P=0.379         P=0.324N       |     P=0.368N        P=0.495         P=0.734        |
|COCHRAN-ARMITAGE       |     P=0.153N                                       |     P=0.608N                                       |
|FISHER EXACT           |                     P=0.340         P=0.248N       |                     P=0.495         P=0.748        |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  14
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         6.25 PPM        20 PPM        |      CONTROL         6.25 PPM        20 PPM        |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     4/70 (6%)       2/70 (3%)       0/70 (0%)      |
|ADJUSTED (b)           |                                                    |      7.6%            5.8%            0.0%          |
|INTERIM SACRIFICE 1 (c)|                                                    |     2/10 (20%)      0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|                                                    |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |                                                    |     1/37 (3%)       1/33 (3%)       0/24 (0%)      |
|FIRST INCIDENCE (DAYS) |                                                    |      282 (I)         732             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.076N        P=0.363N        P=0.084N       |
|INCIDENTAL TUMOR       |                                                    |     P=0.050N*       P=0.352N        P=0.078N       |
|LOGISTIC REGRESSION    |                                                    |     P=0.047N*       P=0.331N        P=0.049N*      |
|COCHRAN-ARMITAGE       |                                                    |     P=0.050N                                       |
|FISHER EXACT           |                                                    |                     P=0.340N        P=0.060N       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangioma                                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/70 (1%)       1/70 (1%)       0/70 (0%)      |     2/70 (3%)       2/70 (3%)       1/70 (1%)      |
|ADJUSTED (b)           |      2.9%            2.6%            0.0%          |      5.1%            5.0%            4.2%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     1/35 (3%)       1/39 (3%)       0/24 (0%)      |     1/37 (3%)       0/33 (0%)       1/24 (4%)      |
|FIRST INCIDENCE (DAYS) |      734 (T)         734 (T)         ---           |      708             572             734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.439N        P=0.738N        P=0.575N       |     P=0.547N        P=0.667         P=0.657N       |
|INCIDENTAL TUMOR       |     P=0.439N        P=0.738N        P=0.575N       |     P=0.349N        P=0.675N        P=0.514N       |
|LOGISTIC REGRESSION    |     P=0.439N        P=0.738N        P=0.575N       |     P=0.472N        P=0.685         P=0.618N       |
|COCHRAN-ARMITAGE       |     P=0.355N                                       |     P=0.406N                                       |
|FISHER EXACT           |                     P=0.752N        P=0.500N       |                     P=0.690N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  15
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         6.25 PPM        20 PPM        |      CONTROL         6.25 PPM        20 PPM        |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/70 (1%)       4/70 (6%)       3/70 (4%)      |     3/70 (4%)       2/70 (3%)       2/70 (3%)      |
|ADJUSTED (b)           |      2.9%            9.4%            9.8%          |      8.1%            5.2%            8.3%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     1/35 (3%)       2/39 (5%)       1/24 (4%)      |     3/37 (8%)       1/33 (3%)       2/24 (8%)      |
|FIRST INCIDENCE (DAYS) |      734 (T)         587             585           |      734 (T)         572             734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.222         P=0.219         P=0.219        |     P=0.624         P=0.543N        P=0.671        |
|INCIDENTAL TUMOR       |     P=0.461         P=0.203         P=0.357        |     P=0.626N        P=0.562N        P=0.671        |
|LOGISTIC REGRESSION    |     P=0.296         P=0.200         P=0.262        |     P=0.572N        P=0.514N        P=0.671        |
|COCHRAN-ARMITAGE       |     P=0.363                                        |     P=0.466N                                       |
|FISHER EXACT           |                     P=0.183         P=0.310        |                     P=0.500N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/70 (3%)       5/70 (7%)       3/70 (4%)      |     5/70 (7%)       3/70 (4%)       3/70 (4%)      |
|ADJUSTED (b)           |      5.7%           11.9%            9.8%          |     13.0%            7.9%           12.5%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     2/35 (6%)       3/39 (8%)       1/24 (4%)      |     4/37 (11%)      1/33 (3%)       3/24 (13%)     |
|FIRST INCIDENCE (DAYS) |      734 (T)         587             585           |      708             572             734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.367         P=0.267         P=0.372        |     P=0.571N        P=0.409N        P=0.611N       |
|INCIDENTAL TUMOR       |     P=0.600         P=0.252         P=0.521        |     P=0.429N        P=0.373N        P=0.519N       |
|LOGISTIC REGRESSION    |     P=0.460         P=0.249         P=0.434        |     P=0.489N        P=0.375N        P=0.591N       |
|COCHRAN-ARMITAGE       |     P=0.548                                        |     P=0.347N                                       |
|FISHER EXACT           |                     P=0.221         P=0.500        |                     P=0.359N        P=0.359N       |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  16
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         6.25 PPM        20 PPM        |      CONTROL         6.25 PPM        20 PPM        |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Histiocytic Sarcoma                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/70 (0%)       0/70 (0%)       4/70 (6%)      |     3/70 (4%)       2/70 (3%)       7/70 (10%)     |
|ADJUSTED (b)           |      0.0%            0.0%           10.6%          |      6.9%            4.5%           20.0%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     0/35 (0%)       0/39 (0%)       0/24 (0%)      |     0/37 (0%)       0/33 (0%)       1/24 (4%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             531           |      485             467             492           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.006 **        (e)           P=0.051        |     P=0.032 *       P=0.518N        P=0.077        |
|INCIDENTAL TUMOR       |     P=0.051           (e)           P=0.148        |     P=0.256         P=0.290N        P=0.425        |
|LOGISTIC REGRESSION    |     P=0.010 **        (e)           P=0.061        |     P=0.213         P=0.501N        P=0.345        |
|COCHRAN-ARMITAGE       |     P=0.011 *                                      |     P=0.074                                        |
|FISHER EXACT           |                       (e)           P=0.060        |                     P=0.500N        P=0.163        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma And Histiocytic Sarcoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/70 (6%)       2/70 (3%)       8/70 (11%)     |    10/70 (14%)     14/70 (20%)     18/70 (26%)     |
|ADJUSTED (b)           |      9.8%            5.1%           21.2%          |     21.9%           37.0%           52.1%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     1/10 (10%)      0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     1/35 (3%)       2/39 (5%)       2/24 (8%)      |     3/37 (8%)      10/33 (30%)      9/24 (38%)     |
|FIRST INCIDENCE (DAYS) |      511             734 (T)         456           |      457 (I)         467             492           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.034 *       P=0.302N        P=0.118        |     P=0.005 **      P=0.195         P=0.010 **     |
|INCIDENTAL TUMOR       |     P=0.146         P=0.388N        P=0.288        |     P=0.086         P=0.302         P=0.128        |
|LOGISTIC REGRESSION    |     P=0.167         P=0.317N        P=0.327        |     P=0.022 *       P=0.223         P=0.030 *      |
|COCHRAN-ARMITAGE       |     P=0.077                                        |     P=0.066                                        |
|FISHER EXACT           |                     P=0.340N        P=0.183        |                     P=0.251         P=0.069        |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  17
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         6.25 PPM        20 PPM        |      CONTROL         6.25 PPM        20 PPM        |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        |
|     NOS, or Undifferentiated Cell Type                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/70 (6%)       2/70 (3%)       4/70 (6%)      |     7/70 (10%)     12/70 (17%)     11/70 (16%)     |
|ADJUSTED (b)           |      9.8%            5.1%           11.8%          |     16.0%           34.0%           38.7%          |
|INTERIM SACRIFICE 1 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       0/10 (0%)       0/10 (0%)      |     1/10 (10%)      0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |     1/35 (3%)       2/39 (5%)       2/24 (8%)      |     3/37 (8%)      10/33 (30%)      8/24 (33%)     |
|FIRST INCIDENCE (DAYS) |      511             734 (T)         456           |      457 (I)         695             533           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.391         P=0.302N        P=0.528        |     P=0.052         P=0.115         P=0.057        |
|INCIDENTAL TUMOR       |     P=0.563         P=0.388N        P=0.613N       |     P=0.178         P=0.140         P=0.187        |
|LOGISTIC REGRESSION    |     P=0.494         P=0.317N        P=0.621        |     P=0.122         P=0.136         P=0.127        |
|COCHRAN-ARMITAGE       |     P=0.529                                        |     P=0.273                                        |
|FISHER EXACT           |                     P=0.340N        P=0.641N       |                     P=0.162         P=0.225        |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    42/70 (60%)     36/70 (51%)     41/70 (59%)     |    33/70 (47%)     38/70 (54%)     25/70 (36%)     |
|ADJUSTED (b)           |     81.5%           81.5%           79.5%          |     69.1%           88.0%           68.9%          |
|INTERIM SACRIFICE 1 (c)|     4/10 (40%)      1/10 (10%)      2/10 (20%)     |     2/10 (20%)      0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     2/10 (20%)      0/10 (0%)       5/10 (50%)     |     3/10 (30%)      2/10 (20%)      1/10 (10%)     |
|TERMINAL (d)           |    26/35 (74%)     31/39 (79%)     14/24 (58%)     |    23/37 (62%)     28/33 (85%)     14/24 (58%)     |
|FIRST INCIDENCE (DAYS) |      281 (I)         281 (I)         281 (I)       |      282 (I)         457 (I)         365           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.037 *       P=0.067N        P=0.136        |     P=0.468         P=0.105         P=0.453        |
|INCIDENTAL TUMOR       |     P=0.408         P=0.115N        P=0.475N       |     P=0.140N        P=0.156         P=0.230N       |
|LOGISTIC REGRESSION    |     P=0.357         P=0.087N        P=0.543        |     P=0.147N        P=0.172         P=0.232N       |
|COCHRAN-ARMITAGE       |     P=0.521                                        |     P=0.056N                                       |
|FISHER EXACT           |                     P=0.198N        P=0.500N       |                     P=0.250         P=0.115N       |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  18
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      CONTROL         6.25 PPM        20 PPM        |      CONTROL         6.25 PPM        20 PPM        |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    20/70 (29%)     27/70 (39%)     34/70 (49%)     |    16/70 (23%)     32/70 (46%)     40/70 (57%)     |
|ADJUSTED (b)           |     43.3%           58.1%           78.4%          |     35.0%           70.7%           85.1%          |
|INTERIM SACRIFICE 1 (c)|     1/10 (10%)      0/10 (0%)       0/10 (0%)      |     0/10 (0%)       0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     0/10 (0%)       1/10 (10%)      0/10 (0%)      |     1/10 (10%)      0/10 (0%)       0/10 (0%)      |
|TERMINAL (d)           |    10/35 (29%)     20/39 (51%)     15/24 (63%)     |     8/37 (22%)     20/33 (61%)     17/24 (71%)     |
|FIRST INCIDENCE (DAYS) |      281 (I)         456 (I)         456           |      457 (I)         467             492           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P<0.001 **      P=0.263         P=0.001 **     |     P<0.001 **      P=0.003 **      P<0.001 **     |
|INCIDENTAL TUMOR       |     P=0.015 *       P=0.122         P=0.019 *      |     P<0.001 **      P=0.002 **      P<0.001 **     |
|LOGISTIC REGRESSION    |     P=0.010 *       P=0.174         P=0.012 *      |     P<0.001 **      P=0.001 **      P<0.001 **     |
|COCHRAN-ARMITAGE       |     P=0.012 *                                      |     P<0.001 **                                     |
|FISHER EXACT           |                     P=0.141         P=0.012 *      |                     P=0.004 **      P<0.001 **     |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    51/70 (73%)     42/70 (60%)     52/70 (74%)     |    40/70 (57%)     49/70 (70%)     44/70 (63%)     |
|ADJUSTED (b)           |     90.8%           87.3%           92.7%          |     77.9%           98.0%           89.7%          |
|INTERIM SACRIFICE 1 (c)|     5/10 (50%)      1/10 (10%)      2/10 (20%)     |     2/10 (20%)      0/10 (0%)       0/10 (0%)      |
|INTERIM SACRIFICE 2 (c)|     2/10 (20%)      1/10 (10%)      5/10 (50%)     |     3/10 (30%)      2/10 (20%)      1/10 (10%)     |
|TERMINAL (d)           |    30/35 (86%)     33/39 (85%)     20/24 (83%)     |    26/37 (70%)     32/33 (97%)     19/24 (79%)     |
|FIRST INCIDENCE (DAYS) |      281 (I)         281 (I)         281 (I)       |      282 (I)         457 (I)         365           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.007 **      P=0.023N*       P=0.052        |     P=0.006 **      P=0.031 *       P=0.009 **     |
|INCIDENTAL TUMOR       |     P=0.261         P=0.032N*       P=0.556        |     P=0.313         P=0.025 *       P=0.325        |
|LOGISTIC REGRESSION    |     P=0.156         P=0.026N*       P=0.380        |     P=0.101         P=0.022 *       P=0.085        |
|COCHRAN-ARMITAGE       |     P=0.316                                        |     P=0.394                                        |
|FISHER EXACT           |                     P=0.076N        P=0.500        |                     P=0.080         P=0.302        |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  19
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
 
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (c)  Observed incidence at interim kill.
          Male interim sacrifices(days):   281  456
          Female interim sacrifices(days): 282  457
 (d)  Observed incidence at terminal kill.
 (f)  Beneath the control incidence are the P-values associated with the trend 
      test.  Beneath the dosed group incidence are the P-values corresponding to 
      pairwise comparisons between the controls and that dosed group.  The life
      table analysis regards tumors in animals dying  prior to terminal kill as
      being (directly or indirectly) the cause of death.  The incidental tumor 
      test regards these lesions as non-fatal.  Logistic regression is an alternative
      method for analyzing the incidence of non-fatal tumors.  The Cochran-Armitage
      and Fisher's exact tests compare directly the overall incidence rates.  
      For all tests, a negative trend is indicated by "N".
 (e)  Value of Statistic cannot be computed. 
 (I)  Interim sacrifice
 (T)  Terminal sacrifice
  #   Tumor rates based on number of animals necropsied.
 
  *   To the right of any statistical result, indicates significance at (P<=0.05).
  **  To the right of any statistical result, indicates significance at (P<=0.01).
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Northwest                                 1,3 BUTADIENE (BUTADIENE)                              DATE: 09/21/94       
EXPERIMENT: 05134 TEST: 02                                                                                     TIME: 14:25:01       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01ES5510500          ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                                             NTP C#: 50602C       
PATHOLOGIST: R. MILLER                                                                                         CAS: 106-99-0        
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                          HIGH DOSE GROUPS                                                          
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE 001    CONTROL                                                                       
                                       INCLUDE 002    CONTROL                                                                       
                                       INCLUDE 007    62.5 PPM                                                                      
                                       INCLUDE 008    62.5 PPM                                                                      
                                       INCLUDE 009    200 PPM                                                                       
                                       INCLUDE 010    200 PPM                                                                       
                                       INCLUDE 011    625 PPM                                                                       
                                       INCLUDE 012    625 PPM                                                                       
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: Battelle Northwest                                 1,3 BUTADIENE (BUTADIENE)                              DATE: 09/21/94      
EXPERIMENT: 05134 TEST: 02                                                                                     TIME: 14:25:01      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01ES5510500          ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                                             NTP C#: 50602C      
PATHOLOGIST: R. MILLER                                                                                         CAS: 106-99-0       
 
 
 
 
 
                                                    MICE(B6C3F1)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Gland
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Gallbladder
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Larynx
                                                    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: Battelle Northwest                                 1,3 BUTADIENE (BUTADIENE)                              DATE: 09/21/94       
EXPERIMENT: 05134 TEST: 02                                                                                     TIME: 14:25:01       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01ES5510500          ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                                             NTP C#: 50602C       
PATHOLOGIST: R. MILLER                                                                                         CAS: 106-99-0        
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                   IN THE ANALYSIS OF THE STUDY OF 1,3 BUTADIENE (BUTADIENE)
 
              ====================================================================================================
 
                                                           MALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Adrenal Medulla               Pheochromocytoma Benign
                             Clitoral/Preputial Gland      Carcinoma
                             Harderian Gland               Adenoma
                                                           Carcinoma or Adenoma
                             Heart                         Hemangiosarcoma
                             Intestine Small               Carcinoma
                                                           Carcinoma or Adenoma
                             Kidney: Renal Tubule          Carcinoma or Adenoma
                             Liver                         Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Lung                          Alveolar/Bronchiolar Adenoma
                                                           Alveolar/Bronchiolar Carcinoma
                                                           Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
                             Stomach, Forestomach          Squamous Cell Carcinoma
                                                           Squamous Cell Carcinoma or Papilloma Squamous
                                                           Squamous Cell Papilloma
                             All Organs                    Hemangiosarcoma
                                                           Hemangiosarcoma or Hemangioma
                                                           Histiocytic Sarcoma
                                                           Malignant Lymphoma And Histiocytic Sarcoma
                                                           Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,
                                                            NOS, or Undifferentiated Cell Type
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
 
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Northwest                                 1,3 BUTADIENE (BUTADIENE)                              DATE: 09/21/94       
EXPERIMENT: 05134 TEST: 02                                                                                     TIME: 14:25:01       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01ES5510500          ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                                             NTP C#: 50602C       
PATHOLOGIST: R. MILLER                                                                                         CAS: 106-99-0        
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                   IN THE ANALYSIS OF THE STUDY OF 1,3 BUTADIENE (BUTADIENE)
 
              ====================================================================================================
 
                                                           FEMALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Adrenal Cortex                Adenoma
                             Adrenal Medulla               Pheochromocytoma Benign
                             Harderian Gland               Adenoma
                                                           Carcinoma
                                                           Carcinoma or Adenoma
                             Heart                         Hemangiosarcoma
                             Islets, Pancreatic            Adenoma
                             Kidney: Renal Tubule          Adenoma
                                                           Carcinoma or Adenoma
                             Liver                         Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Lung                          Alveolar/Bronchiolar Adenoma
                                                           Alveolar/Bronchiolar Carcinoma
                                                           Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
                             Mammary Gland                 Adenoacanthoma
                                                           Carcinoma
                                                           Mixed Tumor Malignant
                             Ovary                         Granulosa Cell Tumor Benign
                                                           Granulosa Cell Tumor Malignant
                                                           Granulosa Cell Tumor, Benign, Malignant, NOS
                                                           Mixed Tumor Benign
                             Pituitary Gland: Pars Distalis or Unspecified Site
                                                           Adenoma
                                                           Carcinoma or Adenoma
                             Skin: Subcutaneous Tissue     Hemangiosarcoma
                                                           Neurofibrosarcoma, Fibrosarcoma, Sarcoma,
                                                            Neurofibroma, or Fibroma
                                                           Neurofibrosarcoma, Fibrosarcoma, or Sarcoma
                                                           Sarcoma
                             Spleen                        Hemangiosarcoma
                             Stomach, Forestomach          Squamous Cell Carcinoma
                                                           Squamous Cell Carcinoma or Papilloma Squamous
                                                           Squamous Cell Papilloma
                             Thyroid Gland: Follicular Cell
                                                           Adenoma
                             Uterus                        Carcinoma
                                                           Polyp Stromal
                                                           Sarcoma Stromal or Polyp Stromal
                             Zymbal's Gland                Carcinoma or Adenoma
                             All Organs                    Hemangiosarcoma
                                                           Hemangiosarcoma or Hemangioma
                                                           Histiocytic Sarcoma
                                                           Malignant Lymphoma And Histiocytic Sarcoma
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Northwest                                 1,3 BUTADIENE (BUTADIENE)                              DATE: 09/21/94       
EXPERIMENT: 05134 TEST: 02                                                                                     TIME: 14:25:01       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01ES5510500          ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                                             NTP C#: 50602C       
PATHOLOGIST: R. MILLER                                                                                         CAS: 106-99-0        
 
                                                           Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,
                                                            NOS, or Undifferentiated Cell Type
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
 
              ====================================================================================================
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   1
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    1/67 (1%)    0/68 (0%)    0/90 (0%)  |  1/70 (1%)    0/69 (0%)    3/70 (4%)    0/88 (0%)  |
|ADJUSTED (b)           |   5.1%         3.4%         0.0%         0.0%      |   2.7%         0.0%        18.8%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  1/35 (3%)    0/22 (0%)    0/4 (0%)     0/0        |  1/37 (3%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   596          680          ---          ---       |   733 (T)      ---          370          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.885N     P=0.601N     P=0.535N       (e)      |  P=0.300      P=0.740N     P=0.024 *      (e)      |
|INCIDENTAL TUMOR       |  P=0.484N     P=0.449N     P=0.171N       (e)      |  P=0.563N     P=0.740N     P=0.515        (e)      |
|LOGISTIC REGRESSION    |  P=0.551N     P=0.553N     P=0.371N     P=0.881N   |  P=0.608N     P=0.740N     P=0.237        (e)      |
|COCHRAN-ARMITAGE       |  P=0.141N                                          |  P=0.365N                                          |
|FISHER EXACT           |               P=0.517N     P=0.255N     P=0.190N   |               P=0.504N     P=0.310      P=0.443N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/64 (0%)    0/64 (0%)    1/86 (1%)  |  0/70 (0%)    0/65 (0%)    2/70 (3%)    0/86 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         7.7%      |   0.0%         0.0%        15.4%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  0/35 (0%)    0/21 (0%)    0/4 (0%)     0/0        |  0/37 (0%)    0/10 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          376       |   ---          ---          543          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.035 *      (e)          (e)        P=0.200    |  P=0.168        (e)        P=0.030 *      (e)      |
|INCIDENTAL TUMOR       |  P=0.183        (e)          (e)        P=0.500    |  P=0.781N       (e)        P=0.561        (e)      |
|LOGISTIC REGRESSION    |  P=0.369        (e)          (e)        P=0.673    |  P=0.738        (e)        P=0.153        (e)      |
|COCHRAN-ARMITAGE       |  P=0.262                                           |  P=0.630N                                          |
|FISHER EXACT           |                 (e)          (e)        P=0.551    |                 (e)        P=0.248        (e)      |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   2
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/27 (0%)    0/29 (0%)    5/26 (19%)   0/19 (0%)  |  0/20 (0%)    0/20 (0%)    0/20 (0%)    0/10 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%       100.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  0/5 (0%)     0/3 (0%)     1/1 (100%)   0/0        |  0/0          0/0          0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   ---          ---          596          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)        P<0.001 **     (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.023 *      (e)        P=0.028 *      (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.050        (e)        P=0.003 **     (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.619                                           |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.023 *      (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  6/70 (9%)   23/70 (33%)  33/70 (47%)   9/90 (10%) | 10/70 (14%)  16/70 (23%)  23/70 (33%)  10/90 (11%) |
|ADJUSTED (b)           |  14.8%        66.0%        95.6%        61.5%      |  23.5%        61.7%        89.8%        40.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/8 (13%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    4/10 (40%)   3/10 (30%)   3/7 (43%)  |  2/10 (20%)   1/10 (10%)   3/10 (30%)   0/2 (0%)   |
|TERMINAL (d)           |  2/35 (6%)   12/22 (55%)   3/4 (75%)    0/0        |  7/37 (19%)   4/11 (36%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   543          456 (I)      382          289       |   457 (I)      457 (I)      370          282 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.003 **   P<0.001 **   P<0.001 **   P=0.071    |  P=0.423      P=0.089      P=0.023 *    P=0.491    |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P=0.014 *  |  P=0.043 *    P=0.032 *    P=0.020 *    P=0.235    |
|COCHRAN-ARMITAGE       |  P=0.022N*                                         |  P=0.069N                                          |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P=0.490    |               P=0.139      P=0.008 **   P=0.357N   |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   3
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    3/70 (4%)    2/70 (3%)    0/90 (0%)  |  0/70 (0%)    0/70 (0%)    1/70 (1%)    0/90 (0%)  |
|ADJUSTED (b)           |   0.0%        11.7%         6.3%         0.0%      |   0.0%         0.0%        50.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  0/35 (0%)    1/22 (5%)    0/4 (0%)     0/0        |  0/37 (0%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   ---          680          495          ---       |   ---          ---          695          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.227      P=0.067      P=0.166        (e)      |  P=0.800        (e)        P=0.016 *      (e)      |
|INCIDENTAL TUMOR       |  P=0.787      P=0.166      P=0.509        (e)      |  P=0.907        (e)        P=0.362        (e)      |
|LOGISTIC REGRESSION    |  P=0.728      P=0.082      P=0.238        (e)      |  P=0.811        (e)        P=0.090        (e)      |
|COCHRAN-ARMITAGE       |  P=0.217N                                          |  P=0.739N                                          |
|FISHER EXACT           |               P=0.122      P=0.248        (e)      |                 (e)        P=0.500        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  6/70 (9%)   24/70 (34%)  34/70 (49%)   9/90 (10%) | 10/70 (14%)  16/70 (23%)  23/70 (33%)  10/90 (11%) |
|ADJUSTED (b)           |  14.8%        67.4%        95.8%        61.5%      |  23.5%        61.7%        89.8%        40.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/8 (13%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    4/10 (40%)   3/10 (30%)   3/7 (43%)  |  2/10 (20%)   1/10 (10%)   3/10 (30%)   0/2 (0%)   |
|TERMINAL (d)           |  2/35 (6%)   12/22 (55%)   3/4 (75%)    0/0        |  7/37 (19%)   4/11 (36%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   543          456 (I)      382          289       |   457 (I)      457 (I)      370          282 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.004 **   P<0.001 **   P<0.001 **   P=0.071    |  P=0.423      P=0.089      P=0.023 *    P=0.491    |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P=0.014 *  |  P=0.043 *    P=0.032 *    P=0.020 *    P=0.235    |
|COCHRAN-ARMITAGE       |  P=0.017N*                                         |  P=0.069N                                          |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P=0.490    |               P=0.139      P=0.008 **   P=0.357N   |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   4
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart                                                                                                                            |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    5/68 (7%)   21/68 (31%)   7/90 (8%)  |  0/70 (0%)    1/69 (1%)   22/70 (31%)  25/90 (28%) |
|ADJUSTED (b)           |   0.0%        19.4%        93.4%        55.9%      |   0.0%         4.0%       100.0%       100.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    1/10 (10%)   3/7 (43%)  |  0/10 (0%)    0/10 (0%)    1/10 (10%)   2/2 (100%) |
|TERMINAL (d)           |  0/35 (0%)    3/22 (14%)   3/4 (75%)    0/0        |  0/37 (0%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   ---          649          456 (I)      289       |   ---          649          343          307       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.011 *    P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.392      P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.028 *    P<0.001 **   P=0.018 *  |  P<0.001 **   P=0.682      P=0.006 **   P=0.005 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.017 *    P<0.001 **   P=0.003 ** |  P<0.001 **   P=0.453      P<0.001 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.383                                           |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.027 *    P<0.001 **   P=0.016 *  |               P=0.496      P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small                                                                                                                  |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    1/70 (1%)    2/70 (3%)    0/90 (0%)  |  0/70 (0%)    1/70 (1%)    0/70 (0%)    0/90 (0%)  |
|ADJUSTED (b)           |   0.0%         4.5%        28.3%         0.0%      |   0.0%         4.3%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  0/35 (0%)    1/22 (5%)    1/4 (25%)    0/0        |  0/37 (0%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   ---          733 (T)      596          ---       |   ---          653          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.147      P=0.407      P=0.032 *      (e)      |  P=1.000      P=0.375        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.391      P=0.407      P=0.121        (e)      |  P=1.000N     P=0.682        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.398      P=0.407      P=0.091        (e)      |  P=0.975N     P=0.451        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.436N                                          |  P=0.541N                                          |
|FISHER EXACT           |               P=0.500      P=0.248        (e)      |               P=0.500        (e)          (e)      |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   5
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small: Jejunum                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    1/70 (1%)    2/70 (3%)    0/90 (0%)  |  0/70 (0%)    0/70 (0%)    0/70 (0%)    0/90 (0%)  |
|ADJUSTED (b)           |   0.0%         4.5%        28.3%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  0/35 (0%)    1/22 (5%)    1/4 (25%)    0/0        |  0/37 (0%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   ---          733 (T)      596          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.147      P=0.407      P=0.032 *      (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.391      P=0.407      P=0.121        (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.398      P=0.407      P=0.091        (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.436N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.500      P=0.248        (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/68 (0%)    0/66 (0%)    0/87 (0%)  |  0/69 (0%)    1/67 (1%)    2/69 (3%)    0/88 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         2.8%       100.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  0/35 (0%)    0/22 (0%)    0/4 (0%)     0/0        |  0/37 (0%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          570          502          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.093      P=0.451      P=0.007 **     (e)      |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.768N     P=0.701      P=0.334        (e)      |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.738      P=0.497      P=0.078        (e)      |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.435N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.493      P=0.248        (e)      |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   6
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    2/68 (3%)    1/69 (1%)    1/90 (1%)  |  0/69 (0%)    0/70 (0%)    2/70 (3%)    0/90 (0%)  |
|ADJUSTED (b)           |   0.0%         9.1%         3.7%        14.3%      |   0.0%         0.0%        34.8%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/7 (14%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  0/35 (0%)    2/22 (9%)    0/4 (0%)     0/0        |  0/37 (0%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   ---          733 (T)      573          456 (I)   |   ---          ---          418          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.051      P=0.143      P=0.407      P=0.429    |  P=0.379        (e)        P=0.037 *      (e)      |
|INCIDENTAL TUMOR       |  P=0.093      P=0.143      P=0.831      P=0.429    |  P=0.793        (e)        P=0.334        (e)      |
|LOGISTIC REGRESSION    |  P=0.152      P=0.141      P=0.480      P=0.487    |  P=0.774        (e)        P=0.182        (e)      |
|COCHRAN-ARMITAGE       |  P=0.624N                                          |  P=0.623N                                          |
|FISHER EXACT           |               P=0.241      P=0.496      P=0.563    |                 (e)        P=0.252        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    3/68 (4%)    1/69 (1%)    1/90 (1%)  |  0/69 (0%)    0/70 (0%)    2/70 (3%)    0/90 (0%)  |
|ADJUSTED (b)           |   0.0%        13.6%         3.7%        14.3%      |   0.0%         0.0%        34.8%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/7 (14%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  0/35 (0%)    3/22 (14%)   0/4 (0%)     0/0        |  0/37 (0%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   ---          733 (T)      573          456 (I)   |   ---          ---          418          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.044 *    P=0.053      P=0.407      P=0.429    |  P=0.379        (e)        P=0.037 *      (e)      |
|INCIDENTAL TUMOR       |  P=0.080      P=0.053      P=0.831      P=0.429    |  P=0.793        (e)        P=0.334        (e)      |
|LOGISTIC REGRESSION    |  P=0.126      P=0.053      P=0.480      P=0.487    |  P=0.774        (e)        P=0.182        (e)      |
|COCHRAN-ARMITAGE       |  P=0.482N                                          |  P=0.623N                                          |
|FISHER EXACT           |               P=0.117      P=0.496      P=0.563    |                 (e)        P=0.252        (e)      |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   7
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 19/70 (27%)  19/68 (28%)  29/68 (43%)   9/89 (10%) | 12/69 (17%)  15/70 (21%)  15/70 (21%)   2/90 (2%)  |
|ADJUSTED (b)           |  37.9%        59.2%        92.8%        65.9%      |  30.9%        66.4%        89.6%        66.7%      |
|INTERIM SACRIFICE 1 (c)|  4/10 (40%)   0/10 (0%)    1/10 (10%)   1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   3/10 (30%)   4/10 (40%)   3/7 (43%)  |  1/10 (10%)   1/10 (10%)   3/10 (30%)   1/2 (50%)  |
|TERMINAL (d)           |  9/35 (26%)  11/22 (50%)   3/4 (75%)    0/0        | 11/37 (30%)   5/11 (45%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   281 (I)      434          281 (I)      281 (I)   |   457 (I)      457 (I)      370          450       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.209      P<0.001 **   P=0.037 *  |  P<0.001 **   P<0.001 **   P<0.001 **   P=0.020 *  |
|INCIDENTAL TUMOR       |  P=0.126      P=0.396      P=0.101      P=0.569    |  P=0.191      P=0.043 *    P=0.007 **   P=0.335    |
|LOGISTIC REGRESSION    |  P=0.332      P=0.503      P=0.022 *    P=0.343N   |  P=0.150      P=0.047 *    P=0.004 **   P=0.469    |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.534      P=0.041 *    P=0.005N** |               P=0.350      P=0.350      P<0.001N** |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 11/70 (16%)  17/68 (25%)  27/68 (40%)   4/89 (4%)  |  4/69 (6%)    9/70 (13%)   9/70 (13%)   1/90 (1%)  |
|ADJUSTED (b)           |  26.0%        58.1%       100.0%        49.2%      |  10.3%        39.9%        83.0%        10.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    1/10 (10%)   3/7 (43%)  |  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/2 (0%)   |
|TERMINAL (d)           |  5/35 (14%)  11/22 (50%)   4/4 (100%)   0/0        |  3/37 (8%)    2/11 (18%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   540          434          351          422       |   677          546          353          418       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.020 *    P<0.001 **   P=0.007 ** |  P<0.001 **   P=0.003 **   P<0.001 **   P=0.157    |
|INCIDENTAL TUMOR       |  P=0.024 *    P=0.102      P=0.010 **   P=0.128    |  P=0.549      P=0.163      P=0.028 *    P=0.948    |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.110      P<0.001 **   P=0.013 *  |  P=0.080      P=0.030 *    P=0.002 **   P=0.664    |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |  P=0.016N*                                         |
|FISHER EXACT           |               P=0.126      P=0.001 **   P=0.016N*  |               P=0.127      P=0.127      P=0.112N   |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   8
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 27/70 (39%)  28/68 (41%)  38/68 (56%)  11/89 (12%) | 16/69 (23%)  20/70 (29%)  19/70 (27%)   3/90 (3%)  |
|ADJUSTED (b)           |  52.4%        80.3%       100.0%        83.0%      |  40.3%        75.3%        92.1%        70.0%      |
|INTERIM SACRIFICE 1 (c)|  4/10 (40%)   0/10 (0%)    1/10 (10%)   1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   3/10 (30%)   4/10 (40%)   5/7 (71%)  |  1/10 (10%)   1/10 (10%)   3/10 (30%)   1/2 (50%)  |
|TERMINAL (d)           | 13/35 (37%)  16/22 (73%)   4/4 (100%)   0/0        | 14/37 (38%)   6/11 (55%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   281 (I)      434          281 (I)      281 (I)   |   457 (I)      457 (I)      353          418       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.092      P<0.001 **   P=0.007 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P=0.001 ** |
|INCIDENTAL TUMOR       |  P=0.064      P=0.332      P=0.104      P=0.419    |  P=0.407      P=0.045 *    P=0.005 **   P=0.306    |
|LOGISTIC REGRESSION    |  P=0.106      P=0.361      P=0.029 *    P=0.514N   |  P=0.114      P=0.026 *    P=0.001 **   P=0.293    |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.445      P=0.031 *    P<0.001N** |               P=0.298      P=0.367      P<0.001N** |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 27/70 (39%)  28/68 (41%)  38/68 (56%)  11/89 (12%) | 16/69 (23%)  20/70 (29%)  19/70 (27%)   3/90 (3%)  |
|ADJUSTED (b)           |  52.4%        80.3%       100.0%        83.0%      |  40.3%        75.3%        92.1%        70.0%      |
|INTERIM SACRIFICE 1 (c)|  4/10 (40%)   0/10 (0%)    1/10 (10%)   1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   3/10 (30%)   4/10 (40%)   5/7 (71%)  |  1/10 (10%)   1/10 (10%)   3/10 (30%)   1/2 (50%)  |
|TERMINAL (d)           | 13/35 (37%)  16/22 (73%)   4/4 (100%)   0/0        | 14/37 (38%)   6/11 (55%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   281 (I)      434          281 (I)      281 (I)   |   457 (I)      457 (I)      353          418       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.092      P<0.001 **   P=0.007 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P=0.001 ** |
|INCIDENTAL TUMOR       |  P=0.064      P=0.332      P=0.104      P=0.419    |  P=0.407      P=0.045 *    P=0.005 **   P=0.306    |
|LOGISTIC REGRESSION    |  P=0.106      P=0.361      P=0.029 *    P=0.514N   |  P=0.114      P=0.026 *    P=0.001 **   P=0.293    |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |  P<0.001N**                                        |
|FISHER EXACT           |               P=0.445      P=0.031 *    P<0.001N** |               P=0.298      P=0.367      P<0.001N** |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   9
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 18/70 (26%)  26/69 (38%)  26/70 (37%)  10/90 (11%) |  4/70 (6%)   20/70 (29%)  18/70 (26%)  19/88 (22%) |
|ADJUSTED (b)           |  46.9%        74.6%       100.0%        78.1%      |  10.5%        66.7%       100.0%        87.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    2/10 (20%)   2/10 (20%) |  0/10 (0%)    0/10 (0%)    2/10 (20%)   1/8 (13%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    1/10 (10%)   3/10 (30%)   5/7 (71%)  |  0/10 (0%)    3/10 (30%)   2/10 (20%)   1/2 (50%)  |
|TERMINAL (d)           | 15/35 (43%)  14/22 (64%)   4/4 (100%)   0/0        |  3/37 (8%)    4/11 (36%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   572          434          281 (I)      251       |   714          443          282 (I)      275       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.002 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.002 **   P=0.020 *    P=0.004 **   P<0.001 ** |  P=0.006 **   P<0.001 **   P=0.011 *    P=0.037 *  |
|LOGISTIC REGRESSION    |  P=0.007 **   P=0.017 *    P=0.004 **   P=0.002 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P=0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |  P=0.200                                           |
|FISHER EXACT           |               P=0.091      P=0.101      P=0.014N*  |               P<0.001 **   P<0.001 **   P=0.004 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  6/70 (9%)   13/69 (19%)  24/70 (34%)   6/90 (7%)  |  0/70 (0%)    9/70 (13%)  20/70 (29%)   8/88 (9%)  |
|ADJUSTED (b)           |  15.5%        44.0%        94.8%        43.9%      |   0.0%        40.8%       100.0%        58.6%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/10 (0%)    0/10 (0%)    1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    1/10 (10%)   2/10 (20%)   2/7 (29%)  |  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/2 (0%)   |
|TERMINAL (d)           |  5/35 (14%)   8/22 (36%)   3/4 (75%)    0/0        |  0/37 (0%)    3/11 (27%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   281 (I)      456 (I)      456 (I)      251       |   ---          532          373          307       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.010 **   P<0.001 **   P=0.007 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.019 *    P<0.001 **   P=0.087    |  P=0.065      P=0.004 **   P<0.001 **   P=0.488    |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.036 *    P<0.001 **   P=0.147    |  P<0.001 **   P<0.001 **   P<0.001 **   P=0.014 *  |
|COCHRAN-ARMITAGE       |  P=0.053N                                          |  P=0.434                                           |
|FISHER EXACT           |               P=0.064      P<0.001 **   P=0.436N   |               P=0.001 **   P<0.001 **   P=0.008 ** |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  10
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 22/70 (31%)  33/69 (48%)  41/70 (59%)  11/90 (12%) |  4/70 (6%)   27/70 (39%)  30/70 (43%)  24/88 (27%) |
|ADJUSTED (b)           |  55.5%        88.2%       100.0%        78.7%      |  10.5%        79.7%       100.0%        91.1%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/10 (0%)    2/10 (20%)   3/10 (30%) |  0/10 (0%)    0/10 (0%)    2/10 (20%)   1/8 (13%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    2/10 (20%)   4/10 (40%)   5/7 (71%)  |  0/10 (0%)    3/10 (30%)   3/10 (30%)   1/2 (50%)  |
|TERMINAL (d)           | 18/35 (51%)  18/22 (82%)   4/4 (100%)   0/0        |  3/37 (8%)    6/11 (55%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   281 (I)      434          281 (I)      251       |   714          443          282 (I)      275       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.003 **   P<0.001 **   P=0.002 ** |  P=0.001 **   P<0.001 **   P<0.001 **   P=0.019 *  |
|LOGISTIC REGRESSION    |  P=0.002 **   P=0.003 **   P<0.001 **   P=0.014 *  |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |  P=0.218                                           |
|FISHER EXACT           |               P=0.035 *    P=0.001 **   P=0.003N** |               P<0.001 **   P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Adenoacanthoma                                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/70 (0%)    0/70 (0%)    0/90 (0%)  |  0/70 (0%)    6/70 (9%)    4/70 (6%)    0/90 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%        32.5%        11.8%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  0/35 (0%)    0/22 (0%)    0/4 (0%)     0/0        |  0/37 (0%)    2/11 (18%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          579          268          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.124      P<0.001 **   P=0.024 *      (e)      |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.144N     P=0.018 *    P=0.787        (e)      |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.409N     P=0.003 **   P=0.132        (e)      |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.084N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.014 *    P=0.060        (e)      |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  11
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/70 (0%)    0/70 (0%)    0/90 (0%)  |  0/70 (0%)    6/70 (9%)   13/70 (19%)  13/90 (14%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%        15.9%        41.0%        83.4%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    2/10 (20%)   1/2 (50%)  |
|TERMINAL (d)           |  0/35 (0%)    0/22 (0%)    0/4 (0%)     0/0        |  0/37 (0%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          392          370          280       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P<0.001 **   P=0.008 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.136      P=0.104      P=0.083      P=0.129    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.002 **   P=0.019 *    P<0.001 **   P=0.002 ** |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.016 *                                         |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.014 *    P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Mixed Tumor Malignant                                                                                                       |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/70 (0%)    0/70 (0%)    0/90 (0%)  |  0/70 (0%)    0/70 (0%)    0/70 (0%)    4/90 (4%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%        23.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  0/35 (0%)    0/22 (0%)    0/4 (0%)     0/0        |  0/37 (0%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          ---          ---          335       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P<0.001 **     (e)          (e)        P=0.002 ** |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.094        (e)          (e)        P=0.834    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.020 *      (e)          (e)        P=0.159    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.006 **                                        |
|FISHER EXACT           |                 (e)          (e)          (e)      |                 (e)          (e)        P=0.097    |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  12
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery                                                                                                                        |
|     Hemangioma                                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    2/70 (3%)    0/70 (0%)    0/90 (0%)  |  0/70 (0%)    0/70 (0%)    0/70 (0%)    0/90 (0%)  |
|ADJUSTED (b)           |   0.0%         8.2%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  0/35 (0%)    1/22 (5%)    0/4 (0%)     0/0        |  0/37 (0%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   ---          707          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.985      P=0.158        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.987N     P=0.255        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.986      P=0.178        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.329N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.248        (e)          (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  2/69 (3%)    3/70 (4%)    1/70 (1%)    1/89 (1%)  |
|ADJUSTED (b)           |                                                    |   5.6%        15.5%         7.7%         1.3%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    1/10 (10%)   0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |                                                    |  2/36 (6%)    1/11 (9%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |                                                    |   733 (T)      457 (I)      543          257       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.144      P=0.159      P=0.242      P=0.522    |
|INCIDENTAL TUMOR       |                                                    |  P=0.624N     P=0.277      P=0.967        (e)      |
|LOGISTIC REGRESSION    |                                                    |  P=0.662      P=0.375      P=0.619      P=0.825    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.221N                                          |
|FISHER EXACT           |                                                    |               P=0.507      P=0.495N     P=0.405N   |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  13
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Granulosa Cell Tumor Benign                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  1/69 (1%)    7/70 (10%)  10/70 (14%)   7/89 (8%)  |
|ADJUSTED (b)           |                                                    |   2.8%        29.8%       100.0%        62.1%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    1/10 (10%)   3/10 (30%)   1/2 (50%)  |
|TERMINAL (d)           |                                                    |  1/36 (3%)    1/11 (9%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |                                                    |   733 (T)      457 (I)      282 (I)      311       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P<0.001 **   P=0.002 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |                                                    |  P=0.018 *    P=0.053      P=0.005 **   P=0.166    |
|LOGISTIC REGRESSION    |                                                    |  P=0.037 *    P=0.013 *    P=0.003 **   P=0.055    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.374                                           |
|FISHER EXACT           |                                                    |               P=0.033 *    P=0.005 **   P=0.068    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Granulosa Cell Tumor Malignant                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  0/69 (0%)    3/70 (4%)    3/70 (4%)    0/89 (0%)  |
|ADJUSTED (b)           |                                                    |   0.0%        19.3%        55.3%         0.0%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/2 (0%)   |
|TERMINAL (d)           |                                                    |  0/36 (0%)    1/11 (9%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |                                                    |   ---          645          457 (I)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.040 *    P=0.018 *    P=0.005 **     (e)      |
|INCIDENTAL TUMOR       |                                                    |  P=0.229      P=0.133      P=0.111        (e)      |
|LOGISTIC REGRESSION    |                                                    |  P=0.479      P=0.042 *    P=0.038 *      (e)      |
|COCHRAN-ARMITAGE       |                                                    |  P=0.215N                                          |
|FISHER EXACT           |                                                    |               P=0.125      P=0.125        (e)      |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  14
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Granulosa Cell Tumor, Benign, Malignant, NOS                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  1/69 (1%)   10/70 (14%)  13/70 (19%)   7/89 (8%)  |
|ADJUSTED (b)           |                                                    |   2.8%        43.9%       100.0%        62.1%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    1/10 (10%)   4/10 (40%)   1/2 (50%)  |
|TERMINAL (d)           |                                                    |  1/36 (3%)    2/11 (18%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |                                                    |   733 (T)      457 (I)      282 (I)      311       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |                                                    |  P=0.006 **   P=0.008 **   P<0.001 **   P=0.166    |
|LOGISTIC REGRESSION    |                                                    |  P=0.018 *    P<0.001 **   P<0.001 **   P=0.055    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.534N                                          |
|FISHER EXACT           |                                                    |               P=0.005 **   P<0.001 **   P=0.068    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Hemangioma                                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  1/69 (1%)    2/70 (3%)    0/70 (0%)    0/89 (0%)  |
|ADJUSTED (b)           |                                                    |   2.8%         6.6%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |                                                    |  1/36 (3%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |                                                    |   733 (T)      594          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.988      P=0.282        (e)          (e)      |
|INCIDENTAL TUMOR       |                                                    |  P=0.865N     P=0.557        (e)          (e)      |
|LOGISTIC REGRESSION    |                                                    |  P=0.732N     P=0.417        (e)          (e)      |
|COCHRAN-ARMITAGE       |                                                    |  P=0.177N                                          |
|FISHER EXACT           |                                                    |               P=0.505      P=0.496N     P=0.437N   |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  15
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Mixed Tumor Benign                                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  0/69 (0%)    2/70 (3%)    6/70 (9%)    1/89 (1%)  |
|ADJUSTED (b)           |                                                    |   0.0%        13.6%       100.0%         2.5%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    0/10 (0%)    1/10 (10%)   0/2 (0%)   |
|TERMINAL (d)           |                                                    |  0/36 (0%)    1/11 (9%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |                                                    |   ---          664          457 (I)      328       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P<0.001 **   P=0.067      P<0.001 **   P=0.419    |
|INCIDENTAL TUMOR       |                                                    |  P=0.441      P=0.186      P=0.067        (e)      |
|LOGISTIC REGRESSION    |                                                    |  P=0.321      P=0.128      P=0.005 **   P=0.785    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.462N                                          |
|FISHER EXACT           |                                                    |               P=0.252      P=0.015 *    P=0.563    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    0/68 (0%)    0/66 (0%)    0/79 (0%)  |  7/70 (10%)   4/67 (6%)    0/68 (0%)    0/81 (0%)  |
|ADJUSTED (b)           |   2.9%         0.0%         0.0%         0.0%      |  17.4%        24.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  1/35 (3%)    0/22 (0%)    0/4 (0%)     0/0        |  5/37 (14%)   2/11 (18%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   733 (T)      ---          ---          ---       |   625          594          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=1.000N     P=0.593N     P=0.905N       (e)      |  P=0.948      P=0.378      P=0.861N       (e)      |
|INCIDENTAL TUMOR       |  P=1.000N     P=0.593N     P=0.905N       (e)      |  P=0.613N     P=0.544N     P=0.254N       (e)      |
|LOGISTIC REGRESSION    |  P=1.000N     P=0.593N     P=0.905N       (e)      |  P=0.501N     P=0.624N     P=0.343N     P=0.845N   |
|COCHRAN-ARMITAGE       |  P=0.463N                                          |  P=0.004N**                                        |
|FISHER EXACT           |               P=0.507N     P=0.515N     P=0.470N   |               P=0.292N     P=0.007N**   P=0.004N** |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  16
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    1/68 (1%)    0/66 (0%)    0/79 (0%)  |  7/70 (10%)   4/67 (6%)    0/68 (0%)    0/81 (0%)  |
|ADJUSTED (b)           |   2.9%         2.2%         0.0%         0.0%      |  17.4%        24.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  1/35 (3%)    0/22 (0%)    0/4 (0%)     0/0        |  5/37 (14%)   2/11 (18%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   733 (T)      464          ---          ---       |   625          594          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.944N     P=0.699      P=0.905N       (e)      |  P=0.948      P=0.378      P=0.861N       (e)      |
|INCIDENTAL TUMOR       |  P=0.563N     P=0.759      P=0.905N       (e)      |  P=0.613N     P=0.544N     P=0.254N       (e)      |
|LOGISTIC REGRESSION    |  P=0.503N     P=0.753      P=0.905N       (e)      |  P=0.501N     P=0.624N     P=0.343N     P=0.845N   |
|COCHRAN-ARMITAGE       |  P=0.289N                                          |  P=0.004N**                                        |
|FISHER EXACT           |               P=0.745      P=0.515N     P=0.470N   |               P=0.292N     P=0.007N**   P=0.004N** |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/70 (0%)    3/70 (4%)    0/90 (0%)  |  1/70 (1%)    2/70 (3%)    2/70 (3%)    2/90 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%        11.7%         0.0%      |   2.7%        13.2%        21.4%         5.7%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  0/35 (0%)    0/22 (0%)    0/4 (0%)     0/0        |  1/37 (3%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   ---          ---          530          ---       |   733 (T)      665          569          328       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.101        (e)        P=0.051        (e)      |  P<0.001 **   P=0.173      P=0.014 *    P=0.130    |
|INCIDENTAL TUMOR       |  P=0.697        (e)        P=0.419        (e)      |  P=0.387      P=0.583      P=0.371        (e)      |
|LOGISTIC REGRESSION    |  P=0.640        (e)        P=0.094        (e)      |  P=0.120      P=0.292      P=0.166      P=0.523    |
|COCHRAN-ARMITAGE       |  P=0.560N                                          |  P=0.605                                           |
|FISHER EXACT           |                 (e)        P=0.122        (e)      |               P=0.500      P=0.500      P=0.594    |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  17
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    0/70 (0%)    0/70 (0%)    0/90 (0%)  |  1/70 (1%)    5/70 (7%)    3/70 (4%)    4/90 (4%)  |
|ADJUSTED (b)           |   2.3%         0.0%         0.0%         0.0%      |   2.4%        20.3%        43.0%        58.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/2 (50%)  |
|TERMINAL (d)           |  0/35 (0%)    0/22 (0%)    0/4 (0%)     0/0        |  0/37 (0%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   572          ---          ---          ---       |   677          597          524          316       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.964N     P=0.529N     P=0.597N       (e)      |  P<0.001 **   P=0.017 *    P=0.002 **   P=0.001 ** |
|INCIDENTAL TUMOR       |  P=0.794N     P=0.419N     P=0.169N       (e)      |  P=0.027 *    P=0.399      P=0.380      P=0.177    |
|LOGISTIC REGRESSION    |  P=0.631N     P=0.499N     P=0.518N     P=0.821N   |  P=0.004 **   P=0.424      P=0.074      P=0.163    |
|COCHRAN-ARMITAGE       |  P=0.444N                                          |  P=0.515                                           |
|FISHER EXACT           |               P=0.500N     P=0.500N     P=0.438N   |               P=0.104      P=0.310      P=0.272    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    0/70 (0%)    0/70 (0%)    0/90 (0%)  |  1/70 (1%)    5/70 (7%)    3/70 (4%)    4/90 (4%)  |
|ADJUSTED (b)           |   2.3%         0.0%         0.0%         0.0%      |   2.4%        20.3%        43.0%        58.3%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/2 (50%)  |
|TERMINAL (d)           |  0/35 (0%)    0/22 (0%)    0/4 (0%)     0/0        |  0/37 (0%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   572          ---          ---          ---       |   677          597          524          316       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.964N     P=0.529N     P=0.597N       (e)      |  P<0.001 **   P=0.017 *    P=0.002 **   P=0.001 ** |
|INCIDENTAL TUMOR       |  P=0.794N     P=0.419N     P=0.169N       (e)      |  P=0.027 *    P=0.399      P=0.380      P=0.177    |
|LOGISTIC REGRESSION    |  P=0.631N     P=0.499N     P=0.518N     P=0.821N   |  P=0.004 **   P=0.424      P=0.074      P=0.163    |
|COCHRAN-ARMITAGE       |  P=0.444N                                          |  P=0.515                                           |
|FISHER EXACT           |               P=0.500N     P=0.500N     P=0.438N   |               P=0.104      P=0.310      P=0.272    |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  18
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Sarcoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    0/70 (0%)    0/70 (0%)    0/90 (0%)  |  1/70 (1%)    5/70 (7%)    3/70 (4%)    3/90 (3%)  |
|ADJUSTED (b)           |   2.3%         0.0%         0.0%         0.0%      |   2.4%        20.3%        43.0%        16.6%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  0/35 (0%)    0/22 (0%)    0/4 (0%)     0/0        |  0/37 (0%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   572          ---          ---          ---       |   677          597          524          316       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.964N     P=0.529N     P=0.597N       (e)      |  P<0.001 **   P=0.017 *    P=0.002 **   P=0.011 *  |
|INCIDENTAL TUMOR       |  P=0.794N     P=0.419N     P=0.169N       (e)      |  P=0.176      P=0.399      P=0.380      P=0.834    |
|LOGISTIC REGRESSION    |  P=0.631N     P=0.499N     P=0.518N     P=0.821N   |  P=0.026 *    P=0.424      P=0.074      P=0.353    |
|COCHRAN-ARMITAGE       |  P=0.444N                                          |  P=0.507N                                          |
|FISHER EXACT           |               P=0.500N     P=0.500N     P=0.438N   |               P=0.104      P=0.310      P=0.410    |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/68 (0%)    1/66 (2%)    0/87 (0%)  |  2/69 (3%)    0/68 (0%)    0/70 (0%)    1/88 (1%)  |
|ADJUSTED (b)           |   0.0%         0.0%         3.0%         0.0%      |   5.4%         0.0%         0.0%        10.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  0/35 (0%)    0/22 (0%)    0/4 (0%)     0/0        |  2/37 (5%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   ---          ---          568          ---       |   733 (T)      ---          ---          418       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.866        (e)        P=0.443        (e)      |  P=0.038 *    P=0.528N       (e)        P=0.157    |
|INCIDENTAL TUMOR       |  P=0.980        (e)        P=0.823        (e)      |  P=0.397      P=0.528N       (e)        P=0.948    |
|LOGISTIC REGRESSION    |  P=0.877        (e)        P=0.476        (e)      |  P=0.300      P=0.528N       (e)        P=0.596    |
|COCHRAN-ARMITAGE       |  P=0.741N                                          |  P=0.583N                                          |
|FISHER EXACT           |                 (e)        P=0.485        (e)      |               P=0.252N     P=0.245N     P=0.409N   |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  19
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    0/70 (0%)    2/70 (3%)    4/90 (4%)  |  0/70 (0%)    1/70 (1%)    1/70 (1%)    7/90 (8%)  |
|ADJUSTED (b)           |   0.0%         0.0%         7.7%        36.6%      |   0.0%         8.3%         3.8%        75.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    1/10 (10%)   2/7 (29%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/2 (50%)  |
|TERMINAL (d)           |  0/35 (0%)    0/22 (0%)    0/4 (0%)     0/0        |  0/37 (0%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   ---          ---          456 (I)      302       |   ---          723          472          275       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)        P=0.148      P=0.007 ** |  P<0.001 **   P=0.277      P=0.374      P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.006 **     (e)        P=0.401      P=0.087    |  P=0.001 **   P=0.682      P=0.967      P=0.141    |
|LOGISTIC REGRESSION    |  P=0.015 *      (e)        P=0.238      P=0.041 *  |  P<0.001 **   P=0.329      P=0.561      P=0.015 *  |
|COCHRAN-ARMITAGE       |  P=0.027 *                                         |  P=0.002 **                                        |
|FISHER EXACT           |                 (e)        P=0.248      P=0.097    |               P=0.500      P=0.500      P=0.016 *  |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    1/70 (1%)    9/70 (13%)   8/90 (9%)  |  0/70 (0%)    3/70 (4%)    6/70 (9%)   23/90 (26%) |
|ADJUSTED (b)           |   2.5%         4.5%        55.4%        58.7%      |   0.0%        18.2%       100.0%        92.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    1/10 (10%)   3/7 (43%)  |  0/10 (0%)    1/10 (10%)   2/10 (20%)   1/2 (50%)  |
|TERMINAL (d)           |  0/35 (0%)    1/22 (5%)    1/4 (25%)    0/0        |  0/37 (0%)    1/11 (9%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   652          733 (T)      456 (I)      281 (I)   |   ---          457 (I)      457 (I)      246       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.679      P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.026 *    P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.745N     P=0.050 *    P=0.005 ** |  P<0.001 **   P=0.092      P=0.072      P=0.041 *  |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.723      P=0.002 **   P=0.010 *  |  P<0.001 **   P=0.086      P=0.012 *    P<0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.037 *                                         |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.752N     P=0.009 **   P=0.041 *  |               P=0.122      P=0.014 *    P<0.001 ** |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  20
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    1/70 (1%)    7/70 (10%)   4/90 (4%)  |  0/70 (0%)    2/70 (3%)    5/70 (7%)   16/90 (18%) |
|ADJUSTED (b)           |   2.5%         4.5%        51.7%        30.3%      |   0.0%        10.8%       100.0%        67.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/7 (14%)  |  0/10 (0%)    1/10 (10%)   2/10 (20%)   0/2 (0%)   |
|TERMINAL (d)           |  0/35 (0%)    1/22 (5%)    1/4 (25%)    0/0        |  0/37 (0%)    1/11 (9%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   652          733 (T)      530          281 (I)   |   ---          457 (I)      457 (I)      246       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.679      P<0.001 **   P=0.005 ** |  P<0.001 **   P=0.119      P=0.002 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.745N     P=0.100      P=0.060    |  P<0.001 **   P=0.119      P=0.076      P=0.399    |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.723      P=0.005 **   P=0.093    |  P<0.001 **   P=0.224      P=0.021 *    P=0.002 ** |
|COCHRAN-ARMITAGE       |  P=0.284                                           |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.752N     P=0.031 *    P=0.272    |               P=0.248      P=0.029 *    P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)    4/68 (6%)    2/67 (3%)    0/87 (0%)  |  1/70 (1%)    2/69 (3%)    2/69 (3%)    1/88 (1%)  |
|ADJUSTED (b)           |   5.7%        17.4%        12.5%         0.0%      |   2.4%        11.5%       100.0%         3.2%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  2/35 (6%)    3/22 (14%)   0/4 (0%)     0/0        |  0/37 (0%)    1/11 (9%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   733 (T)      716          623          ---       |   677          569          569          353       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.250      P=0.155      P=0.163        (e)      |  P=0.004 **   P=0.249      P=0.005 **   P=0.368    |
|INCIDENTAL TUMOR       |  P=0.774      P=0.216      P=0.728        (e)      |  P=0.470      P=0.567      P=0.404        (e)      |
|LOGISTIC REGRESSION    |  P=0.575      P=0.182      P=0.394        (e)      |  P=0.287      P=0.401      P=0.110      P=0.801    |
|COCHRAN-ARMITAGE       |  P=0.060N                                          |  P=0.424N                                          |
|FISHER EXACT           |               P=0.327      P=0.674      P=0.197N   |               P=0.495      P=0.495      P=0.691N   |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  21
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  0/70 (0%)    2/70 (3%)    1/70 (1%)    0/90 (0%)  |
|ADJUSTED (b)           |                                                    |   0.0%        18.2%        50.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |                                                    |  0/37 (0%)    2/11 (18%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |                                                    |   ---          733 (T)      695          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.144      P=0.038 *    P=0.016 *      (e)      |
|INCIDENTAL TUMOR       |                                                    |  P=0.386      P=0.038 *    P=0.362        (e)      |
|LOGISTIC REGRESSION    |                                                    |  P=0.307      P=0.038 *    P=0.090        (e)      |
|COCHRAN-ARMITAGE       |                                                    |  P=0.318N                                          |
|FISHER EXACT           |                                                    |               P=0.248      P=0.500        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  4/70 (6%)    3/70 (4%)    1/70 (1%)    4/90 (4%)  |
|ADJUSTED (b)           |                                                    |   7.6%         6.5%        50.0%       100.0%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  2/10 (20%)   0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    2/10 (20%)   0/10 (0%)    2/2 (100%) |
|TERMINAL (d)           |                                                    |  1/37 (3%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |                                                    |   282 (I)      457 (I)      695          319       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.004 **   P=0.640N     P=0.685N     P=0.050 *  |
|INCIDENTAL TUMOR       |                                                    |  P=0.121      P=0.466N     P=0.310N     P=0.346    |
|LOGISTIC REGRESSION    |                                                    |  P=0.605      P=0.419N     P=0.146N     P=0.502N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.553N                                          |
|FISHER EXACT           |                                                    |               P=0.500N     P=0.183N     P=0.494N   |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  22
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  4/70 (6%)    4/70 (6%)    1/70 (1%)    4/90 (4%)  |
|ADJUSTED (b)           |                                                    |   7.6%        10.0%        50.0%       100.0%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  2/10 (20%)   0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/10 (0%)    2/10 (20%)   0/10 (0%)    2/2 (100%) |
|TERMINAL (d)           |                                                    |  1/37 (3%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |                                                    |   282 (I)      457 (I)      695          319       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.004 **   P=0.478      P=0.685N     P=0.050 *  |
|INCIDENTAL TUMOR       |                                                    |  P=0.138      P=0.564N     P=0.310N     P=0.346    |
|LOGISTIC REGRESSION    |                                                    |  P=0.618      P=0.573N     P=0.146N     P=0.502N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.469N                                          |
|FISHER EXACT           |                                                    |               P=0.641N     P=0.183N     P=0.494N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    0/70 (0%)    0/70 (0%)    0/90 (0%)  |  0/70 (0%)    0/70 (0%)    0/70 (0%)    2/90 (2%)  |
|ADJUSTED (b)           |   2.9%         0.0%         0.0%         0.0%      |   0.0%         0.0%         0.0%        37.5%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  1/35 (3%)    0/22 (0%)    0/4 (0%)     0/0        |  0/37 (0%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   733 (T)      ---          ---          ---       |   ---          ---          ---          387       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=1.000N     P=0.593N     P=0.905N       (e)      |  P<0.001 **     (e)          (e)        P=0.004 ** |
|INCIDENTAL TUMOR       |  P=1.000N     P=0.593N     P=0.905N       (e)      |  P=0.110        (e)          (e)        P=0.834    |
|LOGISTIC REGRESSION    |  P=1.000N     P=0.593N     P=0.905N       (e)      |  P=0.073        (e)          (e)        P=0.287    |
|COCHRAN-ARMITAGE       |  P=0.444N                                          |  P=0.067                                           |
|FISHER EXACT           |               P=0.500N     P=0.500N     P=0.438N   |                 (e)          (e)        P=0.315    |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  23
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangioma                                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    4/70 (6%)    0/70 (0%)    0/90 (0%)  |  2/70 (3%)    4/70 (6%)    1/70 (1%)    0/90 (0%)  |
|ADJUSTED (b)           |   2.9%        17.0%         0.0%         0.0%      |   5.1%        16.3%         2.1%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  1/35 (3%)    3/22 (14%)   0/4 (0%)     0/0        |  1/37 (3%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   733 (T)      707          ---          ---       |   708          594          411          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.892      P=0.075      P=0.905N       (e)      |  P=0.554      P=0.078      P=0.455        (e)      |
|INCIDENTAL TUMOR       |  P=0.937      P=0.111      P=0.905N       (e)      |  P=0.411N     P=0.592      P=0.666N       (e)      |
|LOGISTIC REGRESSION    |  P=0.922      P=0.091      P=0.905N       (e)      |  P=0.487N     P=0.195      P=0.780N       (e)      |
|COCHRAN-ARMITAGE       |  P=0.084N                                          |  P=0.054N                                          |
|FISHER EXACT           |               P=0.183      P=0.500N     P=0.438N   |               P=0.340      P=0.500N     P=0.190N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/70 (1%)    7/70 (10%)  25/70 (36%)   7/90 (8%)  |  3/70 (4%)    5/70 (7%)   24/70 (34%)  29/90 (32%) |
|ADJUSTED (b)           |   2.9%        26.6%        94.4%        55.9%      |   8.1%        31.8%       100.0%       100.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    1/10 (10%)   3/7 (43%)  |  0/10 (0%)    0/10 (0%)    1/10 (10%)   2/2 (100%) |
|TERMINAL (d)           |  1/35 (3%)    4/22 (18%)   3/4 (75%)    0/0        |  3/37 (8%)    2/11 (18%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   733 (T)      649          456 (I)      289       |   733 (T)      649          343          307       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.008 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.021 *    P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.023 *    P<0.001 **   P=0.018 *  |  P<0.001 **   P=0.149      P=0.002 **   P=0.004 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.012 *    P<0.001 **   P=0.003 ** |  P<0.001 **   P=0.075      P<0.001 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.520N                                          |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.031 *    P<0.001 **   P=0.067    |               P=0.359      P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  24
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/70 (3%)   11/70 (16%)  25/70 (36%)   7/90 (8%)  |  5/70 (7%)    9/70 (13%)  25/70 (36%)  29/90 (32%) |
|ADJUSTED (b)           |   5.7%        41.3%        94.4%        55.9%      |  13.0%        42.9%       100.0%       100.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    1/10 (10%)   3/7 (43%)  |  0/10 (0%)    0/10 (0%)    1/10 (10%)   2/2 (100%) |
|TERMINAL (d)           |  2/35 (6%)    7/22 (32%)   3/4 (75%)    0/0        |  4/37 (11%)   2/11 (18%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   733 (T)      649          456 (I)      289       |   708          594          343          307       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P=0.003 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.003 **   P<0.001 **   P=0.018 *  |  P<0.001 **   P=0.165      P=0.005 **   P=0.004 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.001 **   P<0.001 **   P=0.004 ** |  P<0.001 **   P=0.027 *    P<0.001 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.281N                                          |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.008 **   P<0.001 **   P=0.161    |               P=0.199      P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Histiocytic Sarcoma                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/70 (0%)    5/70 (7%)    7/70 (10%)   4/90 (4%)  |  3/70 (4%)    4/70 (6%)    7/70 (10%)   4/90 (4%)  |
|ADJUSTED (b)           |   0.0%        14.0%        31.4%         8.0%      |   6.9%        17.7%        27.4%         9.8%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/10 (0%)  |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/8 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/7 (0%)   |  0/10 (0%)    0/10 (0%)    0/10 (0%)    0/2 (0%)   |
|TERMINAL (d)           |  0/35 (0%)    1/22 (5%)    0/4 (0%)     0/0        |  0/37 (0%)    0/11 (0%)    0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   ---          398          288          120       |   485          524          344          300       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.021 *    P<0.001 **   P=0.044 *  |  P<0.001 **   P=0.195      P=0.002 **   P=0.027 *  |
|INCIDENTAL TUMOR       |  P=0.463N     P=0.046 *    P=0.184        (e)      |  P=0.052N     P=0.168N     P=0.320N     P=0.166N   |
|LOGISTIC REGRESSION    |  P=0.488      P=0.032 *    P=0.009 **   P=0.801    |  P=0.432      P=0.425      P=0.146      P=0.634    |
|COCHRAN-ARMITAGE       |  P=0.492                                           |  P=0.457N                                          |
|FISHER EXACT           |               P=0.029 *    P=0.007 **   P=0.097    |               P=0.500      P=0.163      P=0.637    |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  25
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma And Histiocytic Sarcoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/70 (6%)   11/70 (16%)   9/70 (13%)  58/90 (64%) | 10/70 (14%)  11/70 (16%)  17/70 (24%)  37/90 (41%) |
|ADJUSTED (b)           |   9.8%        29.0%        33.3%        84.7%      |  21.9%        47.0%        55.9%        65.0%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/8 (13%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    2/7 (29%)  |  1/10 (10%)   0/10 (0%)    1/10 (10%)   0/2 (0%)   |
|TERMINAL (d)           |  1/35 (3%)    2/22 (9%)    0/4 (0%)     0/0        |  3/37 (8%)    3/11 (27%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   511          200          171          120       |   457 (I)      407          205          189       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.022 *    P=0.005 **   P<0.001 ** |  P<0.001 **   P=0.041 *    P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.001 **   P=0.167      P=0.478N     P=0.022 *  |  P=0.317N     P=0.266N     P=0.236N     P=0.624N   |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.044 *    P=0.155      P<0.001 ** |  P<0.001 **   P=0.319      P=0.072      P=0.057    |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.049 *    P=0.122      P<0.001 ** |               P=0.500      P=0.099      P<0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                                                                        |
|     NOS, or Undifferentiated Cell Type                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/70 (6%)    6/70 (9%)    2/70 (3%)   54/90 (60%) |  7/70 (10%)   7/70 (10%)  10/70 (14%)  33/90 (37%) |
|ADJUSTED (b)           |   9.8%        17.2%         2.9%        83.4%      |  16.0%        35.6%        39.2%        61.1%      |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/10 (10%) |  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/8 (13%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/10 (0%)    0/10 (0%)    2/7 (29%)  |  1/10 (10%)   0/10 (0%)    1/10 (10%)   0/2 (0%)   |
|TERMINAL (d)           |  1/35 (3%)    1/22 (5%)    0/4 (0%)     0/0        |  3/37 (8%)    3/11 (27%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   511          200          171          161       |   457 (I)      407          205          189       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.238      P=0.628      P<0.001 ** |  P<0.001 **   P=0.110      P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.594N     P=0.049N*    P=0.022 *  |  P=0.325      P=0.596N     P=0.472N     P=0.442    |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.352      P=0.266N     P<0.001 ** |  P<0.001 **   P=0.445      P=0.264      P=0.060    |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.372      P=0.340N     P<0.001 ** |               P=0.610N     P=0.303      P<0.001 ** |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  26
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 42/70 (60%)  45/70 (64%)  52/70 (74%)  21/90 (23%) | 33/70 (47%)  44/70 (63%)  47/70 (67%)  41/90 (46%) |
|ADJUSTED (b)           |  81.5%       100.0%       100.0%        94.4%      |  69.1%        97.6%       100.0%       100.0%      |
|INTERIM SACRIFICE 1 (c)|  4/10 (40%)   0/10 (0%)    3/10 (30%)   3/10 (30%) |  2/10 (20%)   0/10 (0%)    2/10 (20%)   2/8 (25%)  |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   6/10 (60%)   6/10 (60%)   6/7 (86%)  |  3/10 (30%)   6/10 (60%)   9/10 (90%)   2/2 (100%) |
|TERMINAL (d)           | 26/35 (74%)  22/22 (100%)  4/4 (100%)   0/0        | 23/37 (62%)  10/11 (91%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   281 (I)      434          281 (I)      251       |   282 (I)      443          282 (I)      246       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.008 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.004 **   P=0.117      P=0.016 *    P=0.050    |  P=0.001 **   P=0.003 **   P<0.001 **   P=0.050 *  |
|LOGISTIC REGRESSION    |  P=0.018 *    P=0.128      P=0.001 **   P=0.138    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001N**                                        |  P=0.083N                                          |
|FISHER EXACT           |               P=0.364      P=0.052      P<0.001N** |               P=0.044 *    P=0.013 *    P=0.484N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 20/70 (29%)  43/70 (61%)  50/70 (71%)  66/90 (73%) | 16/70 (23%)  42/70 (60%)  56/70 (80%)  74/90 (82%) |
|ADJUSTED (b)           |  43.3%        91.1%       100.0%        97.5%      |  35.0%        92.8%       100.0%       100.0%      |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/10 (0%)    0/10 (0%)    2/10 (20%) |  0/10 (0%)    0/10 (0%)    0/10 (0%)    1/8 (13%)  |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    1/10 (10%)   4/10 (40%)   6/7 (86%)  |  1/10 (10%)   0/10 (0%)    7/10 (70%)   2/2 (100%) |
|TERMINAL (d)           | 10/35 (29%)  18/22 (82%)   4/4 (100%)   0/0        |  8/37 (22%)   8/11 (73%)   0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   281 (I)      200          171          120       |   457 (I)      392          205          189       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P<0.001 **   P<0.001 **   P<0.001 **   P=0.001 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P=0.001 ** |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |  P<0.001 **                                        |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P<0.001 ** |               P<0.001 **   P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  27
                          STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |   CONTROL      62.5 PPM     200 PPM      625 PPM   |
|                       |                                                    |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 51/70 (73%)  54/70 (77%)  58/70 (83%)  74/90 (82%) | 40/70 (57%)  54/70 (77%)  61/70 (87%)  77/90 (86%) |
|ADJUSTED (b)           |  90.8%       100.0%       100.0%       100.0%      |  77.9%       100.0%       100.0%       100.0%      |
|INTERIM SACRIFICE 1 (c)|  5/10 (50%)   0/10 (0%)    3/10 (30%)   5/10 (50%) |  2/10 (20%)   0/10 (0%)    2/10 (20%)   3/8 (38%)  |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   6/10 (60%)   6/10 (60%)   7/7 (100%) |  3/10 (30%)   6/10 (60%)  10/10 (100%)  2/2 (100%) |
|TERMINAL (d)           | 30/35 (86%)  22/22 (100%)  4/4 (100%)   0/0        | 26/37 (70%)  11/11 (100%)  0/0          0/0        |
|FIRST INCIDENCE (DAYS) |   281 (I)      200          171          120       |   282 (I)      392          205          189       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **   P=0.008 **   P<0.001 **   P<0.001 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|INCIDENTAL TUMOR       |  P=0.001 **   P=0.281      P=0.172      P=0.020 *  |  P<0.001 **   P=0.006 **   P<0.001 **   P=0.025 *  |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.114      P=0.006 **   P<0.001 ** |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.127                                           |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.348      P=0.111      P=0.110    |               P=0.009 **   P<0.001 **   P<0.001 ** |
|=================================================================================================================================|
 
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (c)  Observed incidence at interim kill.
          Male interim sacrifices(days):   281  456
          Female interim sacrifices(days): 282  457
 (d)  Observed incidence at terminal kill.
 (f)  Beneath the control incidence are the P-values associated with the trend 
      test.  Beneath the dosed group incidence are the P-values corresponding to 
      pairwise comparisons between the controls and that dosed group.  The life
      table analysis regards tumors in animals dying  prior to terminal kill as
      being (directly or indirectly) the cause of death.  The incidental tumor 
      test regards these lesions as non-fatal.  Logistic regression is an alternative
      method for analyzing the incidence of non-fatal tumors.  The Cochran-Armitage
      and Fisher's exact tests compare directly the overall incidence rates.  
      For all tests, a negative trend is indicated by "N".
 (e)  Value of Statistic cannot be computed. 
 (I)  Interim sacrifice
 (T)  Terminal sacrifice
  #   Tumor rates based on number of animals necropsied.
 
  *   To the right of any statistical result, indicates significance at (P<=0.05).
  **  To the right of any statistical result, indicates significance at (P<=0.01).
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Northwest                                 1,3 BUTADIENE (BUTADIENE)                              DATE: 09/21/94       
EXPERIMENT: 05134 TEST: 02                                                                                     TIME: 14:36:36       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01ES5510500          ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                                             NTP C#: 50602C       
PATHOLOGIST: R. MILLER                                                                                         CAS: 106-99-0        
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                           STOP EXPOSURES                                                           
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE 001    CONTROL                                                                       
                                       INCLUDE 013    200 PPM SE40                                                                  
                                       INCLUDE 014    312 PPM SE52                                                                  
                                       INCLUDE 015    625 PPM SE13                                                                  
                                       INCLUDE 016    625 PPM SE 26                                                                 
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: Battelle Northwest                                 1,3 BUTADIENE (BUTADIENE)                              DATE: 09/21/94      
EXPERIMENT: 05134 TEST: 02                                                                                     TIME: 14:36:36      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01ES5510500          ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                                             NTP C#: 50602C      
PATHOLOGIST: R. MILLER                                                                                         CAS: 106-99-0       
 
 
 
 
 
                                                    MICE(B6C3F1)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Gland
                                                    Bone Marrow
                                                    Brain
                                                    Epididymis
                                                    Gallbladder
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Larynx
                                                    Liver
                                                    Lung
                                                    Nose
                                                    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: Battelle Northwest                                 1,3 BUTADIENE (BUTADIENE)                              DATE: 09/21/94       
EXPERIMENT: 05134 TEST: 02                                                                                     TIME: 14:36:36       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01ES5510500          ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                                             NTP C#: 50602C       
PATHOLOGIST: R. MILLER                                                                                         CAS: 106-99-0        
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                   IN THE ANALYSIS OF THE STUDY OF 1,3 BUTADIENE (BUTADIENE)
 
              ====================================================================================================
 
                                                           MALE MICE
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Adrenal Medulla               Pheochromocytoma Benign
                             All Organs                    Hemangioma
                                                           Hemangiosarcoma
                                                           Hemangiosarcoma or Hemangioma
                                                           Histiocytic Sarcoma
                                                           Malignant Lymphoma And Histiocytic Sarcoma
                                                           Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,
                                                            NOS, or Undifferentiated Cell Type
                                                           Benign Tumors
                                                           Malignant Tumors
                                                           Malignant and Benign Tumors
                             Brain                         Glioma Malignant
                                                           Neuroblastoma Malignant
                             Clitoral/Preputial Gland      Carcinoma
                                                           Carcinoma or Adenoma
                             Harderian Gland               Adenoma
                                                           Carcinoma
                                                           Carcinoma or Adenoma
                             Heart                         Hemangiosarcoma
                             Kidney: Renal Tubule          Adenoma
                             Liver                         Hemangiosarcoma
                                                           Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma
                                                           Hepatocellular Carcinoma or Hepatoblastoma
                                                           Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Lung                          Alveolar/Bronchiolar Adenoma
                                                           Alveolar/Bronchiolar Carcinoma
                                                           Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
                             Mesentery                     Hemangioma
                             Stomach, Forestomach          Squamous Cell Carcinoma
                                                           Squamous Cell Carcinoma or Papilloma Squamous
                                                           Squamous Cell Papilloma
                             Thyroid Gland: Follicular Cell
                                                           Adenoma
                             Zymbal's Gland                Carcinoma
                                                           Carcinoma or Adenoma
 
              ====================================================================================================
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   1
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|Adrenal Cortex                                                                |
|     Adenoma                                                                  |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            |  2/70 (3%)    1/45 (2%)    0/49 (0%)    1/100 (1%)   |
|ADJUSTED (b)           |   5.1%         5.0%         0.0%         4.0%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  1/35 (3%)    0/9 (0%)     0/1 (0%)     0/5 (0%)     |
|FIRST INCIDENCE (DAYS) |   596          651          ---          566         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P=0.533      P=0.701      P=0.716N     P=0.654      |
|INCIDENTAL TUMOR       |  P=0.322N     P=0.435N     P=0.274N     P=0.327N     |
|LOGISTIC REGRESSION    |  P=0.508N     P=0.678N     P=0.487N     P=0.639N     |
|COCHRAN-ARMITAGE       |  P=0.255N                                            |
|FISHER EXACT           |               P=0.662N     P=0.344N     P=0.368N     |
|==============================================================================|
|                                                                              |
|Adrenal Medulla                                                               |
|     Pheochromocytoma Benign                                                  |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            |  0/70 (0%)    0/45 (0%)    1/48 (2%)    2/97 (2%)    |
|ADJUSTED (b)           |   0.0%         0.0%         3.3%        23.3%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  0/35 (0%)    0/9 (0%)     0/1 (0%)     1/5 (20%)    |
|FIRST INCIDENCE (DAYS) |   ---          ---          449          567         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P=0.017 *      (e)        P=0.365      P=0.039 *    |
|INCIDENTAL TUMOR       |  P=0.061        (e)        P=0.781      P=0.138      |
|LOGISTIC REGRESSION    |  P=0.078        (e)        P=0.466      P=0.116      |
|COCHRAN-ARMITAGE       |  P=0.164                                             |
|FISHER EXACT           |                 (e)        P=0.407      P=0.336      |
|==============================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   2
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|Bone Marrow                                                                   |
|     Mast Cell Tumor NOS                                                      |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            |  1/70 (1%)    3/50 (6%)    1/49 (2%)    1/97 (1%)    |
|ADJUSTED (b)           |   2.4%        15.6%        20.0%         2.1%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  0/35 (0%)    0/9 (0%)     0/1 (0%)     0/5 (0%)     |
|FIRST INCIDENCE (DAYS) |   609          555          649          429         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P=0.356      P=0.117      P=0.348      P=0.646      |
|INCIDENTAL TUMOR       |  P=0.287N     P=0.669      P=0.679N     P=0.439N     |
|LOGISTIC REGRESSION    |  P=0.570N     P=0.179      P=0.593      P=0.738N     |
|COCHRAN-ARMITAGE       |  P=0.344N                                            |
|FISHER EXACT           |               P=0.195      P=0.656      P=0.664N     |
|==============================================================================|
|                                                                              |
|Brain                                                                         |
|     Glioma Malignant                                                         |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            |  0/70 (0%)    0/50 (0%)    0/50 (0%)    3/100 (3%)   |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%        14.8%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  0/35 (0%)    0/9 (0%)     0/1 (0%)     0/5 (0%)     |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          544         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P=0.005 **     (e)          (e)        P=0.037 *    |
|INCIDENTAL TUMOR       |  P=0.029 *      (e)          (e)        P=0.334      |
|LOGISTIC REGRESSION    |  P=0.011 *      (e)          (e)        P=0.078      |
|COCHRAN-ARMITAGE       |  P=0.044 *                                           |
|FISHER EXACT           |                 (e)          (e)        P=0.201      |
|==============================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   3
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|Brain                                                                         |
|     Neuroblastoma Malignant                                                  |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            |  0/70 (0%)    0/50 (0%)    0/50 (0%)    2/100 (2%)   |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         6.2%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  0/35 (0%)    0/9 (0%)     0/1 (0%)     0/5 (0%)     |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          342         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P=0.039 *      (e)          (e)        P=0.165      |
|INCIDENTAL TUMOR       |  P=0.280        (e)          (e)        P=0.805      |
|LOGISTIC REGRESSION    |  P=0.118        (e)          (e)        P=0.341      |
|COCHRAN-ARMITAGE       |  P=0.107                                             |
|FISHER EXACT           |                 (e)          (e)        P=0.345      |
|==============================================================================|
|                                                                              |
|Clitoral/Preputial Gland                                                      |
|     Carcinoma                                                                |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            |  0/27 (0%)    1/8 (13%)    4/4 (100%)   7/16 (44%)   |
|ADJUSTED (b)           |   0.0%        10.0%       100.0%         0.0%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  0/5 (0%)     0/2 (0%)     1/1 (100%)   0/0          |
|FIRST INCIDENCE (DAYS) |   ---          699          639          520         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P=0.247      P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P=0.183      P=0.718      P=0.028 *    P=0.545      |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.421      P=0.001 **   P=0.002 **   |
|COCHRAN-ARMITAGE       |  P<0.001 **                                          |
|FISHER EXACT           |               P=0.229      P<0.001 **   P<0.001 **   |
|==============================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   4
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|Clitoral/Preputial Gland                                                      |
|     Carcinoma or Adenoma                                                     |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            |  0/27 (0%)    1/8 (13%)    4/4 (100%)   8/16 (50%)   |
|ADJUSTED (b)           |   0.0%        10.0%       100.0%         0.0%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  0/5 (0%)     0/2 (0%)     1/1 (100%)   0/0          |
|FIRST INCIDENCE (DAYS) |   ---          699          639          520         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P=0.247      P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P=0.128      P=0.718      P=0.028 *    P=0.455      |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.421      P=0.001 **   P<0.001 **   |
|COCHRAN-ARMITAGE       |  P<0.001 **                                          |
|FISHER EXACT           |               P=0.229      P<0.001 **   P<0.001 **   |
|==============================================================================|
|                                                                              |
|Harderian Gland                                                               |
|     Adenoma                                                                  |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #          |
|-----------            |                                                      |
|OVERALL (a)            |  6/70 (9%)   26/50 (52%)  28/50 (56%)  33/100 (33%)  |
|ADJUSTED (b)           |  14.8%        87.9%       100.0%        95.9%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  2/35 (6%)    6/9 (67%)    1/1 (100%)   4/5 (80%)    |
|FIRST INCIDENCE (DAYS) |   543          440          344          306         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P<0.001 **   P<0.001 **   P=0.002 **   P<0.001 **   |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|COCHRAN-ARMITAGE       |  P=0.020 *                                           |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P<0.001 **   |
|==============================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   5
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|Harderian Gland                                                               |
|     Carcinoma                                                                |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #          |
|-----------            |                                                      |
|OVERALL (a)            |  0/70 (0%)    2/50 (4%)    2/50 (4%)    4/100 (4%)   |
|ADJUSTED (b)           |   0.0%         5.6%        51.5%        38.7%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  0/35 (0%)    0/9 (0%)     0/1 (0%)     1/5 (20%)    |
|FIRST INCIDENCE (DAYS) |   ---          510          441          567         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P=0.002 **   P=0.182      P=0.021 *    P<0.001 **   |
|INCIDENTAL TUMOR       |  P=0.049 *    P=0.437      P=0.347      P=0.049 *    |
|LOGISTIC REGRESSION    |  P=0.022 *    P=0.168      P=0.127      P=0.007 **   |
|COCHRAN-ARMITAGE       |  P=0.141                                             |
|FISHER EXACT           |               P=0.172      P=0.172      P=0.117      |
|==============================================================================|
|                                                                              |
|Harderian Gland                                                               |
|     Carcinoma or Adenoma                                                     |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #          |
|-----------            |                                                      |
|OVERALL (a)            |  6/70 (9%)   27/50 (54%)  30/50 (60%)  36/100 (36%)  |
|ADJUSTED (b)           |  14.8%        88.3%       100.0%       100.0%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  2/35 (6%)    6/9 (67%)    1/1 (100%)   5/5 (100%)   |
|FIRST INCIDENCE (DAYS) |   543          440          344          306         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|COCHRAN-ARMITAGE       |  P=0.008 **                                          |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P<0.001 **   |
|==============================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   6
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|Heart                                                                         |
|     Hemangiosarcoma                                                          |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            |  0/70 (0%)   15/50 (30%)  33/50 (66%)  20/100 (20%)  |
|ADJUSTED (b)           |   0.0%        76.2%       100.0%        73.3%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  0/35 (0%)    5/9 (56%)    1/1 (100%)   2/5 (40%)    |
|FIRST INCIDENCE (DAYS) |   ---          330          328          306         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P=0.082      P<0.001 **   P<0.001 **   P<0.001 **   |
|LOGISTIC REGRESSION    |  P=0.002 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|COCHRAN-ARMITAGE       |  P=0.028 *                                           |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P<0.001 **   |
|==============================================================================|
|                                                                              |
|Kidney: Renal Tubule                                                          |
|     Adenoma                                                                  |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            |  0/70 (0%)    4/48 (8%)    3/49 (6%)    2/100 (2%)   |
|ADJUSTED (b)           |   0.0%        17.4%        27.8%        16.1%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  0/35 (0%)    0/9 (0%)     0/1 (0%)     0/5 (0%)     |
|FIRST INCIDENCE (DAYS) |   ---          516          539          440         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P=0.089      P=0.016 *    P=0.007 **   P=0.073      |
|INCIDENTAL TUMOR       |  P=0.550N     P=0.234      P=0.275      P=0.410      |
|LOGISTIC REGRESSION    |  P=0.314      P=0.026 *    P=0.044 *    P=0.203      |
|COCHRAN-ARMITAGE       |  P=0.562                                             |
|FISHER EXACT           |               P=0.025 *    P=0.067      P=0.345      |
|==============================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   7
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|Liver                                                                         |
|     Hemangiosarcoma                                                          |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            |  0/70 (0%)    0/49 (0%)    1/50 (2%)    3/99 (3%)    |
|ADJUSTED (b)           |   0.0%         0.0%        16.7%        12.9%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  0/35 (0%)    0/9 (0%)     0/1 (0%)     0/5 (0%)     |
|FIRST INCIDENCE (DAYS) |   ---          ---          639          543         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P=0.005 **     (e)        P=0.136      P=0.040 *    |
|INCIDENTAL TUMOR       |  P=0.108        (e)        P=0.718      P=0.453      |
|LOGISTIC REGRESSION    |  P=0.018 *      (e)        P=0.313      P=0.084      |
|COCHRAN-ARMITAGE       |  P=0.073                                             |
|FISHER EXACT           |                 (e)        P=0.417      P=0.198      |
|==============================================================================|
|                                                                              |
|Liver                                                                         |
|     Hepatocellular Adenoma                                                   |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            | 19/70 (27%)  27/49 (55%)  19/50 (38%)  30/99 (30%)   |
|ADJUSTED (b)           |  37.9%        91.1%       100.0%        93.2%        |
|INTERIM SACRIFICE 1 (c)|  4/10 (40%)   0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   0/0          0/0          0/0          |
|TERMINAL (d)           |  9/35 (26%)   7/9 (78%)    1/1 (100%)   4/5 (80%)    |
|FIRST INCIDENCE (DAYS) |   281 (I)      399          326          313         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P=0.010 **   P=0.002 **   P=0.104      P=0.011 *    |
|LOGISTIC REGRESSION    |  P=0.073      P=0.002 **   P=0.127      P=0.129      |
|COCHRAN-ARMITAGE       |  P=0.361N                                            |
|FISHER EXACT           |               P=0.002 **   P=0.144      P=0.394      |
|==============================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   8
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|Liver                                                                         |
|     Hepatocellular Carcinoma                                                 |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            | 11/70 (16%)  14/49 (29%)  10/50 (20%)  18/99 (18%)   |
|ADJUSTED (b)           |  26.0%        50.3%        74.6%        91.7%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  5/35 (14%)   1/9 (11%)    0/1 (0%)     4/5 (80%)    |
|FIRST INCIDENCE (DAYS) |   540          407          382          483         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P=0.009 **   P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P=0.221      P=0.419N     P=0.308N     P=0.179      |
|LOGISTIC REGRESSION    |  P=0.074      P=0.590      P=0.117      P=0.105      |
|COCHRAN-ARMITAGE       |  P=0.516N                                            |
|FISHER EXACT           |               P=0.072      P=0.355      P=0.419      |
|==============================================================================|
|                                                                              |
|Liver                                                                         |
|     Hepatocellular Carcinoma or Hepatoblastoma                               |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            | 11/70 (16%)  14/49 (29%)  11/50 (22%)  18/99 (18%)   |
|ADJUSTED (b)           |  26.0%        50.3%        77.1%        91.7%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  5/35 (14%)   1/9 (11%)    0/1 (0%)     4/5 (80%)    |
|FIRST INCIDENCE (DAYS) |   540          407          382          483         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P=0.009 **   P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P=0.240      P=0.419N     P=0.370N     P=0.179      |
|LOGISTIC REGRESSION    |  P=0.077      P=0.590      P=0.389      P=0.105      |
|COCHRAN-ARMITAGE       |  P=0.513N                                            |
|FISHER EXACT           |               P=0.072      P=0.260      P=0.419      |
|==============================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE   9
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|Liver                                                                         |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                       |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            | 27/70 (39%)  33/49 (67%)  24/50 (48%)  37/99 (37%)   |
|ADJUSTED (b)           |  52.4%        93.4%       100.0%        95.9%        |
|INTERIM SACRIFICE 1 (c)|  4/10 (40%)   0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   0/0          0/0          0/0          |
|TERMINAL (d)           | 13/35 (37%)   7/9 (78%)    1/1 (100%)   4/5 (80%)    |
|FIRST INCIDENCE (DAYS) |   281 (I)      399          326          313         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P=0.049 *    P=0.022 *    P=0.431      P=0.081      |
|LOGISTIC REGRESSION    |  P=0.077      P=0.002 **   P=0.122      P=0.104      |
|COCHRAN-ARMITAGE       |  P=0.161N                                            |
|FISHER EXACT           |               P=0.002 **   P=0.200      P=0.500N     |
|==============================================================================|
|                                                                              |
|Liver                                                                         |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma      |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            | 27/70 (39%)  33/49 (67%)  25/50 (50%)  37/99 (37%)   |
|ADJUSTED (b)           |  52.4%        93.4%       100.0%        95.9%        |
|INTERIM SACRIFICE 1 (c)|  4/10 (40%)   0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   0/0          0/0          0/0          |
|TERMINAL (d)           | 13/35 (37%)   7/9 (78%)    1/1 (100%)   4/5 (80%)    |
|FIRST INCIDENCE (DAYS) |   281 (I)      399          326          313         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P=0.054      P=0.022 *    P=0.373      P=0.081      |
|LOGISTIC REGRESSION    |  P=0.074      P=0.002 **   P=0.078      P=0.104      |
|COCHRAN-ARMITAGE       |  P=0.160N                                            |
|FISHER EXACT           |               P=0.002 **   P=0.145      P=0.500N     |
|==============================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  10
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|Lung                                                                          |
|     Alveolar/Bronchiolar Adenoma                                             |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            | 18/70 (26%)  24/50 (48%)  26/50 (52%)  29/100 (29%)  |
|ADJUSTED (b)           |  46.9%        94.3%       100.0%        89.3%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           | 15/35 (43%)   8/9 (89%)    1/1 (100%)   3/5 (60%)    |
|FIRST INCIDENCE (DAYS) |   572          399          344          327         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P=0.056      P=0.006 **   P=0.007 **   P=0.036 *    |
|LOGISTIC REGRESSION    |  P=0.008 **   P=0.002 **   P<0.001 **   P<0.001 **   |
|COCHRAN-ARMITAGE       |  P=0.409N                                            |
|FISHER EXACT           |               P=0.010 *    P=0.003 **   P=0.385      |
|==============================================================================|
|                                                                              |
|Lung                                                                          |
|     Alveolar/Bronchiolar Carcinoma                                           |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            |  6/70 (9%)   22/50 (44%)  16/50 (32%)  29/100 (29%)  |
|ADJUSTED (b)           |  15.5%        89.5%       100.0%        90.8%        |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  5/35 (14%)   7/9 (78%)    1/1 (100%)   3/5 (60%)    |
|FIRST INCIDENCE (DAYS) |   281 (I)      481          392          241         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P<0.001 **   P<0.001 **   P=0.002 **   P<0.001 **   |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|COCHRAN-ARMITAGE       |  P=0.027 *                                           |
|FISHER EXACT           |               P<0.001 **   P=0.001 **   P<0.001 **   |
|==============================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  11
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|Lung                                                                          |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma           |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            | 22/70 (31%)  36/50 (72%)  32/50 (64%)  45/100 (45%)  |
|ADJUSTED (b)           |  55.5%       100.0%       100.0%       100.0%        |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           | 18/35 (51%)   9/9 (100%)   1/1 (100%)   5/5 (100%)   |
|FIRST INCIDENCE (DAYS) |   281 (I)      399          344          241         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|COCHRAN-ARMITAGE       |  P=0.297                                             |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P=0.052      |
|==============================================================================|
|                                                                              |
|Mesentery                                                                     |
|     Hemangioma                                                               |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #          |
|-----------            |                                                      |
|OVERALL (a)            |  0/70 (0%)    3/50 (6%)    0/50 (0%)    2/100 (2%)   |
|ADJUSTED (b)           |   0.0%        26.1%         0.0%        40.0%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  0/35 (0%)    2/9 (22%)    0/1 (0%)     2/5 (40%)    |
|FIRST INCIDENCE (DAYS) |   ---          651          ---          729 (T)     |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P=0.005 **   P=0.008 **     (e)        P=0.003 **   |
|INCIDENTAL TUMOR       |  P=0.011 *    P=0.028 *      (e)        P=0.003 **   |
|LOGISTIC REGRESSION    |  P=0.023 *    P=0.023 *      (e)        P=0.003 **   |
|COCHRAN-ARMITAGE       |  P=0.456                                             |
|FISHER EXACT           |               P=0.070        (e)        P=0.345      |
|==============================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  12
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|Stomach, Forestomach                                                          |
|     Squamous Cell Carcinoma                                                  |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #          |
|-----------            |                                                      |
|OVERALL (a)            |  0/70 (0%)    0/50 (0%)    5/50 (10%)  10/100 (10%)  |
|ADJUSTED (b)           |   0.0%         0.0%        33.1%        56.8%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  0/35 (0%)    0/9 (0%)     0/1 (0%)     2/5 (40%)    |
|FIRST INCIDENCE (DAYS) |   ---          ---          422          288         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **     (e)        P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P=0.004 **     (e)        P=0.213      P=0.009 **   |
|LOGISTIC REGRESSION    |  P<0.001 **     (e)        P=0.007 **   P=0.004 **   |
|COCHRAN-ARMITAGE       |  P=0.002 **                                          |
|FISHER EXACT           |                 (e)        P=0.011 *    P=0.004 **   |
|==============================================================================|
|                                                                              |
|Stomach, Forestomach                                                          |
|     Squamous Cell Carcinoma or Papilloma Squamous                            |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #          |
|-----------            |                                                      |
|OVERALL (a)            |  1/70 (1%)    3/50 (6%)    9/50 (18%)  17/100 (17%)  |
|ADJUSTED (b)           |   2.5%        21.4%       100.0%        63.4%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  0/35 (0%)    1/9 (11%)    1/1 (100%)   2/5 (40%)    |
|FIRST INCIDENCE (DAYS) |   652          584          401          288         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P=0.065      P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P=0.003 **   P=0.431      P=0.058      P=0.023 *    |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.148      P<0.001 **   P=0.001 **   |
|COCHRAN-ARMITAGE       |  P<0.001 **                                          |
|FISHER EXACT           |               P=0.195      P=0.002 **   P<0.001 **   |
|==============================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  13
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|Stomach, Forestomach                                                          |
|     Squamous Cell Papilloma                                                  |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #          |
|-----------            |                                                      |
|OVERALL (a)            |  1/70 (1%)    3/50 (6%)    4/50 (8%)    8/100 (8%)   |
|ADJUSTED (b)           |   2.5%        21.4%       100.0%        32.2%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  0/35 (0%)    1/9 (11%)    1/1 (100%)   1/5 (20%)    |
|FIRST INCIDENCE (DAYS) |   652          584          401          327         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P=0.065      P=0.003 **   P=0.002 **   |
|INCIDENTAL TUMOR       |  P=0.057      P=0.431      P=0.223      P=0.254      |
|LOGISTIC REGRESSION    |  P=0.030 *    P=0.148      P=0.070      P=0.057      |
|COCHRAN-ARMITAGE       |  P=0.066                                             |
|FISHER EXACT           |               P=0.195      P=0.096      P=0.057      |
|==============================================================================|
|                                                                              |
|Thyroid Gland: Follicular Cell                                                |
|     Adenoma                                                                  |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |                                                      |
|-----------            |                                                      |
|OVERALL (a)            |  2/70 (3%)    2/48 (4%)    1/49 (2%)    2/99 (2%)    |
|ADJUSTED (b)           |   5.7%        15.3%        25.0%        40.0%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  2/35 (6%)    1/9 (11%)    0/1 (0%)     2/5 (40%)    |
|FIRST INCIDENCE (DAYS) |   729 (T)      650          664          729 (T)     |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P=0.033 *    P=0.257      P=0.171      P=0.058      |
|INCIDENTAL TUMOR       |  P=0.083      P=0.413      P=0.500      P=0.058      |
|LOGISTIC REGRESSION    |  P=0.115      P=0.383      P=0.446      P=0.058      |
|COCHRAN-ARMITAGE       |  P=0.402N                                            |
|FISHER EXACT           |               P=0.538      P=0.632N     P=0.550N     |
|==============================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  14
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|Zymbal's Gland                                                                |
|     Carcinoma                                                                |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #          |
|-----------            |                                                      |
|OVERALL (a)            |  0/70 (0%)    1/50 (2%)    0/50 (0%)    4/100 (4%)   |
|ADJUSTED (b)           |   0.0%         4.8%         0.0%        12.9%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  0/35 (0%)    0/9 (0%)     0/1 (0%)     0/5 (0%)     |
|FIRST INCIDENCE (DAYS) |   ---          650          ---          429         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P=0.004 **   P=0.372        (e)        P=0.026 *    |
|INCIDENTAL TUMOR       |  P=0.048 *    P=0.674        (e)        P=0.347      |
|LOGISTIC REGRESSION    |  P=0.019 *    P=0.412        (e)        P=0.069      |
|COCHRAN-ARMITAGE       |  P=0.051                                             |
|FISHER EXACT           |               P=0.417        (e)        P=0.117      |
|==============================================================================|
|                                                                              |
|Zymbal's Gland                                                                |
|     Carcinoma or Adenoma                                                     |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #          |
|-----------            |                                                      |
|OVERALL (a)            |  1/70 (1%)    1/50 (2%)    0/50 (0%)    4/100 (4%)   |
|ADJUSTED (b)           |   2.9%         4.8%         0.0%        12.9%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  1/35 (3%)    0/9 (0%)     0/1 (0%)     0/5 (0%)     |
|FIRST INCIDENCE (DAYS) |   729 (T)      650          ---          429         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P=0.011 *    P=0.531      P=0.998N     P=0.042 *    |
|INCIDENTAL TUMOR       |  P=0.092      P=0.750      P=0.998N     P=0.414      |
|LOGISTIC REGRESSION    |  P=0.059      P=0.625      P=0.998N     P=0.153      |
|COCHRAN-ARMITAGE       |  P=0.169                                             |
|FISHER EXACT           |               P=0.662      P=0.583N     P=0.314      |
|==============================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  15
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|All Organs                                                                    |
|     Hemangioma                                                               |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #          |
|-----------            |                                                      |
|OVERALL (a)            |  1/70 (1%)    4/50 (8%)    0/50 (0%)    4/100 (4%)   |
|ADJUSTED (b)           |   2.9%        28.8%         0.0%        51.0%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  1/35 (3%)    2/9 (22%)    0/1 (0%)     2/5 (40%)    |
|FIRST INCIDENCE (DAYS) |   729 (T)      595          ---          595         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P=0.012 *    P=0.998N     P<0.001 **   |
|INCIDENTAL TUMOR       |  P=0.016 *    P=0.060      P=0.998N     P=0.020 *    |
|LOGISTIC REGRESSION    |  P=0.013 *    P=0.045 *    P=0.998N     P=0.010 **   |
|COCHRAN-ARMITAGE       |  P=0.391                                             |
|FISHER EXACT           |               P=0.096      P=0.583N     P=0.314      |
|==============================================================================|
|                                                                              |
|All Organs                                                                    |
|     Hemangiosarcoma                                                          |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #          |
|-----------            |                                                      |
|OVERALL (a)            |  1/70 (1%)   17/50 (34%)  34/50 (68%)  26/100 (26%)  |
|ADJUSTED (b)           |   2.9%        78.2%       100.0%        83.0%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  1/35 (3%)    5/9 (56%)    1/1 (100%)   2/5 (40%)    |
|FIRST INCIDENCE (DAYS) |   729 (T)      330          328          306         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P=0.012 *    P<0.001 **   P<0.001 **   P<0.001 **   |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|COCHRAN-ARMITAGE       |  P=0.007 **                                          |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P<0.001 **   |
|==============================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  16
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|All Organs                                                                    |
|     Hemangiosarcoma or Hemangioma                                            |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #          |
|-----------            |                                                      |
|OVERALL (a)            |  2/70 (3%)   20/50 (40%)  34/50 (68%)  28/100 (28%)  |
|ADJUSTED (b)           |   5.7%        85.1%       100.0%        89.2%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  2/35 (6%)    6/9 (67%)    1/1 (100%)   3/5 (60%)    |
|FIRST INCIDENCE (DAYS) |   729 (T)      330          328          306         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P=0.006 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|COCHRAN-ARMITAGE       |  P=0.009 **                                          |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P<0.001 **   |
|==============================================================================|
|                                                                              |
|All Organs                                                                    |
|     Histiocytic Sarcoma                                                      |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #          |
|-----------            |                                                      |
|OVERALL (a)            |  0/70 (0%)    5/50 (10%)   7/50 (14%)   4/100 (4%)   |
|ADJUSTED (b)           |   0.0%        21.3%        43.0%        32.1%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  0/35 (0%)    0/9 (0%)     0/1 (0%)     1/5 (20%)    |
|FIRST INCIDENCE (DAYS) |   ---          576          314          364         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P=0.013 *    P=0.006 **   P<0.001 **   P=0.005 **   |
|INCIDENTAL TUMOR       |  P=0.406N     P=0.171      P=0.160      P=0.080      |
|LOGISTIC REGRESSION    |  P=0.211      P=0.011 *    P=0.005 **   P=0.040 *    |
|COCHRAN-ARMITAGE       |  P=0.377                                             |
|FISHER EXACT           |               P=0.011 *    P=0.002 **   P=0.117      |
|==============================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  17
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|All Organs                                                                    |
|     Malignant Lymphoma And Histiocytic Sarcoma                               |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #          |
|-----------            |                                                      |
|OVERALL (a)            |  4/70 (6%)   13/50 (26%)  15/50 (30%)  59/100 (59%)  |
|ADJUSTED (b)           |   9.8%        46.8%       100.0%        80.7%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  1/35 (3%)    1/9 (11%)    1/1 (100%)   2/5 (40%)    |
|FIRST INCIDENCE (DAYS) |   511          208          217          159         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P=0.003 **   P=0.297      P=0.153      P=0.038 *    |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.002 **   P<0.001 **   P<0.001 **   |
|COCHRAN-ARMITAGE       |  P<0.001 **                                          |
|FISHER EXACT           |               P=0.002 **   P<0.001 **   P<0.001 **   |
|==============================================================================|
|                                                                              |
|All Organs                                                                    |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed,                     |
|     NOS, or Undifferentiated Cell Type                                       |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #          |
|-----------            |                                                      |
|OVERALL (a)            |  4/70 (6%)    8/50 (16%)   8/50 (16%)  55/100 (55%)  |
|ADJUSTED (b)           |   9.8%        32.4%       100.0%        69.7%        |
|INTERIM SACRIFICE 1 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           |  1/35 (3%)    1/9 (11%)    1/1 (100%)   1/5 (20%)    |
|FIRST INCIDENCE (DAYS) |   511          208          217          159         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P=0.016 *    P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P<0.001 **   P=0.640N     P=0.521      P=0.192      |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.064      P=0.013 *    P<0.001 **   |
|COCHRAN-ARMITAGE       |  P<0.001 **                                          |
|FISHER EXACT           |               P=0.062      P=0.062      P<0.001 **   |
|==============================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  18
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|All Organs                                                                    |
|     Benign Tumors                                                            |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #          |
|-----------            |                                                      |
|OVERALL (a)            | 42/70 (60%)  41/50 (82%)  41/50 (82%)  56/100 (56%)  |
|ADJUSTED (b)           |  81.5%       100.0%       100.0%       100.0%        |
|INTERIM SACRIFICE 1 (c)|  4/10 (40%)   0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   0/0          0/0          0/0          |
|TERMINAL (d)           | 26/35 (74%)   9/9 (100%)   1/1 (100%)   5/5 (100%)   |
|FIRST INCIDENCE (DAYS) |   281 (I)      399          326          306         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P=0.006 **   P=0.020 *    P=0.017 *    P=0.005 **   |
|LOGISTIC REGRESSION    |  P<0.001 **   P=0.004 **   P<0.001 **   P=0.001 **   |
|COCHRAN-ARMITAGE       |  P=0.093N                                            |
|FISHER EXACT           |               P=0.008 **   P=0.008 **   P=0.359N     |
|==============================================================================|
|                                                                              |
|All Organs                                                                    |
|     Malignant Tumors                                                         |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #          |
|-----------            |                                                      |
|OVERALL (a)            | 20/70 (29%)  43/50 (86%)  50/50 (100%) 98/100 (98%)  |
|ADJUSTED (b)           |  43.3%        95.3%       100.0%       100.0%        |
|INTERIM SACRIFICE 1 (c)|  1/10 (10%)   0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  0/10 (0%)    0/0          0/0          0/0          |
|TERMINAL (d)           | 10/35 (29%)   7/9 (78%)    1/1 (100%)   5/5 (100%)   |
|FIRST INCIDENCE (DAYS) |   281 (I)      208          217          159         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|COCHRAN-ARMITAGE       |  P<0.001 **                                          |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P<0.001 **   |
|==============================================================================|
 
         DATE: 09/21/94                     EXPERIMENT: 05134 TEST: 02                                                 PAGE  19
STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MALE MICE(B6C3F1) -- 1,3 BUTADIENE (BUTADIENE)
 
                       TERMINAL SACRIFICE AT 105 WEEKS
 
|==============================================================================|
|DOSE                   |   CONTROL      200 PPM      312 PPM      625 PPM     |
|                       |                SE40         SE52         SE 26       |
|==============================================================================|
|                                                                              |
|All Organs                                                                    |
|     Malignant and Benign Tumors                                              |
|                                                                              |
|------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #          |
|-----------            |                                                      |
|OVERALL (a)            | 51/70 (73%)  49/50 (98%)  50/50 (100%) 98/100 (98%)  |
|ADJUSTED (b)           |  90.8%       100.0%       100.0%       100.0%        |
|INTERIM SACRIFICE 1 (c)|  5/10 (50%)   0/0          0/0          0/0          |
|INTERIM SACRIFICE 2 (c)|  2/10 (20%)   0/0          0/0          0/0          |
|TERMINAL (d)           | 30/35 (86%)   9/9 (100%)   1/1 (100%)   5/5 (100%)   |
|FIRST INCIDENCE (DAYS) |   281 (I)      208          217          159         |
|-----------------------|                                                      |
|STATISTICAL TESTS (f)  |                                                      |
|-----------------------|                                                      |
|LIFE TABLE             |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|INCIDENTAL TUMOR       |  P=0.035 *    P=0.105      P=0.198      P=0.137      |
|LOGISTIC REGRESSION    |  P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|COCHRAN-ARMITAGE       |  P<0.001 **                                          |
|FISHER EXACT           |               P<0.001 **   P<0.001 **   P<0.001 **   |
|==============================================================================|
 
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (c)  Observed incidence at interim kill.
          Male interim sacrifices(days):   281  456
          Female interim sacrifices(days):
 (d)  Observed incidence at terminal kill.
 (f)  Beneath the control incidence are the P-values associated with the trend 
      test.  Beneath the dosed group incidence are the P-values corresponding to 
      pairwise comparisons between the controls and that dosed group.  The life
      table analysis regards tumors in animals dying  prior to terminal kill as
      being (directly or indirectly) the cause of death.  The incidental tumor 
      test regards these lesions as non-fatal.  Logistic regression is an alternative
      method for analyzing the incidence of non-fatal tumors.  The Cochran-Armitage
      and Fisher's exact tests compare directly the overall incidence rates.  
      For all tests, a negative trend is indicated by "N".
 (e)  Value of Statistic cannot be computed. 
 (I)  Interim sacrifice
 (T)  Terminal sacrifice
  #   Tumor rates based on number of animals necropsied.
 
  *   To the right of any statistical result, indicates significance at (P<=0.05).
  **  To the right of any statistical result, indicates significance at (P<=0.01).
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.