NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                   RHODAMINE 6G                                     DATE: 09/07/94       
EXPERIMENT: 05048 TEST: 01                                                                                     TIME: 00:08:31       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-28024          ROUTE: DOSED FEED                                                                  NTP C#: 56122        
PATHOLOGIST: H. GILES                                                                                          CAS: 989-38-8        
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08    
LAB: Southern Research Inst                                   RHODAMINE 6G                                     DATE: 09/07/94      
EXPERIMENT: 05048 TEST: 01                                                                                     TIME: 00:08:31      
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                       
CONT: N01-ES-28024          ROUTE: DOSED FEED                                                                  NTP C#: 56122       
PATHOLOGIST: H. GILES                                                                                          CAS: 989-38-8       
 
 
 
 
 
                                                    RATS(FISCHER344)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
 
 
                                                    ----------------
 
                                                    Adrenal Gland
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Southern Research Inst                                   RHODAMINE 6G                                     DATE: 09/07/94       
EXPERIMENT: 05048 TEST: 01                                                                                     TIME: 00:08:31       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-28024          ROUTE: DOSED FEED                                                                  NTP C#: 56122        
PATHOLOGIST: H. GILES                                                                                          CAS: 989-38-8        
 
 
 
 
 
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                          IN THE ANALYSIS OF THE STUDY OF RHODAMINE 6G
 
              ====================================================================================================
 
                                                           MALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Liver                         Hepatocellular Carcinoma or Hepatocellular Adenoma
                                                           Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
                             Skin                          Keratoacanthoma
                                                           Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,
                                                            Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma
                             Thyroid Gland: C-Cell         Carcinoma or Adenoma
                             All Organs                    Malignant Tumors
 
              ====================================================================================================
 
                                                           FEMALE RATS
                                                          -------------
                                 ORGAN                               MORPHOLOGY
                                -------                             ------------
 
                             Adrenal Medulla               Pheochromocytoma Benign
                                                           Pheochromocytoma: Benign, Complex, Malignant, NOS
                             Uterus                        Sarcoma Stromal
 
              ====================================================================================================
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE   1
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       0/49 (0%)       0/50 (0%)      |     1/50 (2%)       3/50 (6%)       0/50 (0%)      |
|ADJUSTED (b)           |      2.2%            0.0%            0.0%          |      3.4%            7.6%            0.0%          |
|TERMINAL (d)           |     0/22 (0%)       0/21 (0%)       0/27 (0%)      |     1/29 (3%)       1/30 (3%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      603             ---             ---           |      734 (T)         638             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.287N        P=0.500N        P=0.504N       |     P=0.376N        P=0.324         P=0.493N       |
|INCIDENTAL TUMOR       |     P=0.428N        P=0.581N        P=0.718N       |     P=0.347N        P=0.349         P=0.493N       |
|LOGISTIC REGRESSION    |     P=0.188N        P=0.438N        P=0.412N       |     P=0.363N        P=0.289         P=0.493N       |
|COCHRAN-ARMITAGE       |     P=0.284N                                       |     P=0.367N                                       |
|FISHER EXACT           |                     P=0.505N        P=0.500N       |                     P=0.309         P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    18/50 (36%)     25/49 (51%)     23/50 (46%)     |     3/50 (6%)       3/50 (6%)       8/50 (16%)     |
|ADJUSTED (b)           |     55.0%           72.0%           61.3%          |     10.3%            8.1%           22.7%          |
|TERMINAL (d)           |     9/22 (41%)     12/21 (57%)     13/27 (48%)     |     3/29 (10%)      1/30 (3%)       4/30 (13%)     |
|FIRST INCIDENCE (DAYS) |      585             639             629           |      734 (T)         638             531           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.435         P=0.101         P=0.435        |     P=0.070         P=0.639N        P=0.120        |
|INCIDENTAL TUMOR       |     P=0.160         P=0.086         P=0.167        |     P=0.048 *       P=0.620N        P=0.067        |
|LOGISTIC REGRESSION    |     P=0.185         P=0.081         P=0.203        |     P=0.053         P=0.644N        P=0.092        |
|COCHRAN-ARMITAGE       |     P=0.191                                        |     P=0.059                                        |
|FISHER EXACT           |                     P=0.096         P=0.208        |                     P=0.661N        P=0.100        |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE   2
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Malignant                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    10/50 (20%)      8/49 (16%)      5/50 (10%)     |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |     34.8%           27.3%           18.5%          |      0.0%            0.0%            6.7%          |
|TERMINAL (d)           |     5/22 (23%)      3/21 (14%)      5/27 (19%)     |     0/29 (0%)       0/30 (0%)       2/30 (7%)      |
|FIRST INCIDENCE (DAYS) |      694             643             733 (T)       |      ---             ---             734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.065N        P=0.459N        P=0.072N       |     P=0.097           (e)           P=0.245        |
|INCIDENTAL TUMOR       |     P=0.100N        P=0.413N        P=0.096N       |     P=0.097           (e)           P=0.245        |
|LOGISTIC REGRESSION    |     P=0.091N        P=0.432N        P=0.097N       |     P=0.097           (e)           P=0.245        |
|COCHRAN-ARMITAGE       |     P=0.107N                                       |     P=0.095                                        |
|FISHER EXACT           |                     P=0.416N        P=0.131N       |                       (e)           P=0.247        |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    23/50 (46%)     27/49 (55%)     26/50 (52%)     |     3/50 (6%)       3/50 (6%)      10/50 (20%)     |
|ADJUSTED (b)           |     67.8%           75.7%           69.6%          |     10.3%            8.1%           28.6%          |
|TERMINAL (d)           |    12/22 (55%)     13/21 (62%)     16/27 (59%)     |     3/29 (10%)      1/30 (3%)       6/30 (20%)     |
|FIRST INCIDENCE (DAYS) |      585             639             629           |      734 (T)         638             531           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.463N        P=0.228         P=0.513N       |     P=0.021 *       P=0.639N        P=0.047 *      |
|INCIDENTAL TUMOR       |     P=0.281         P=0.215         P=0.324        |     P=0.013 *       P=0.620N        P=0.024 *      |
|LOGISTIC REGRESSION    |     P=0.315         P=0.209         P=0.352        |     P=0.014 *       P=0.644N        P=0.032 *      |
|COCHRAN-ARMITAGE       |     P=0.316                                        |     P=0.017 *                                      |
|FISHER EXACT           |                     P=0.241         P=0.345        |                     P=0.661N        P=0.036 *      |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE   3
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Osteosarcoma or Osteoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |     1/50 (2%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            5.9%          |      2.3%            2.0%            0.0%          |
|TERMINAL (d)           |     0/22 (0%)       0/21 (0%)       0/27 (0%)      |     0/29 (0%)       0/30 (0%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             657           |      626             569             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.113           (e)           P=0.266        |     P=0.342N        P=0.748N        P=0.509N       |
|INCIDENTAL TUMOR       |     P=0.073           (e)           P=0.199        |     P=0.193N        P=0.677N        P=0.362N       |
|LOGISTIC REGRESSION    |     P=0.094           (e)           P=0.237        |     P=0.255N        P=0.647         P=0.467N       |
|COCHRAN-ARMITAGE       |     P=0.095                                        |     P=0.334N                                       |
|FISHER EXACT           |                       (e)           P=0.247        |                     P=0.753N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/49 (4%)       3/48 (6%)       2/43 (5%)      |     5/42 (12%)      4/40 (10%)      2/39 (5%)      |
|ADJUSTED (b)           |      6.8%           14.3%            4.4%          |     17.0%           12.5%            5.0%          |
|TERMINAL (d)           |     1/22 (5%)       3/21 (14%)      0/25 (0%)      |     4/27 (15%)      2/24 (8%)       0/25 (0%)      |
|FIRST INCIDENCE (DAYS) |      620             733 (T)         468           |      667             657             623           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.554N        P=0.487         P=0.676N       |     P=0.199N        P=0.537N        P=0.245N       |
|INCIDENTAL TUMOR       |     P=0.554N        P=0.460         P=0.660N       |     P=0.201N        P=0.549N        P=0.238N       |
|LOGISTIC REGRESSION    |     P=0.515         P=0.485         P=0.636        |     P=0.196N        P=0.535N        P=0.247N       |
|COCHRAN-ARMITAGE       |     P=0.547                                        |     P=0.195N                                       |
|FISHER EXACT           |                     P=0.490         P=0.641        |                     P=0.532N        P=0.248N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE   4
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/49 (4%)       4/48 (8%)       4/43 (9%)      |     1/42 (2%)       4/40 (10%)      3/39 (8%)      |
|ADJUSTED (b)           |      4.9%           10.8%           13.1%          |      2.4%           12.7%           10.3%          |
|TERMINAL (d)           |     0/22 (0%)       0/21 (0%)       2/25 (8%)      |     0/27 (0%)       2/24 (8%)       2/25 (8%)      |
|FIRST INCIDENCE (DAYS) |      661             619             667           |      661             603             635           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.310         P=0.298         P=0.367        |     P=0.242         P=0.179         P=0.279        |
|INCIDENTAL TUMOR       |     P=0.182         P=0.335         P=0.300        |     P=0.262         P=0.191         P=0.309        |
|LOGISTIC REGRESSION    |     P=0.191         P=0.337         P=0.265        |     P=0.229         P=0.167         P=0.273        |
|COCHRAN-ARMITAGE       |     P=0.222                                        |     P=0.234                                        |
|FISHER EXACT           |                     P=0.329         P=0.278        |                     P=0.165         P=0.280        |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/49 (8%)       7/48 (15%)      6/43 (14%)     |     6/42 (14%)      8/40 (20%)      5/39 (13%)     |
|ADJUSTED (b)           |     11.3%           23.5%           16.8%          |     19.0%           24.3%           14.8%          |
|TERMINAL (d)           |     1/22 (5%)       3/21 (14%)      2/25 (8%)      |     4/27 (15%)      4/24 (17%)      2/25 (8%)      |
|FIRST INCIDENCE (DAYS) |      620             619             468           |      661             603             623           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.375         P=0.235         P=0.407        |     P=0.485N        P=0.357         P=0.546N       |
|INCIDENTAL TUMOR       |     P=0.265         P=0.242         P=0.374        |     P=0.472N        P=0.356         P=0.521N       |
|LOGISTIC REGRESSION    |     P=0.198         P=0.253         P=0.217        |     P=0.496N        P=0.349         P=0.558N       |
|COCHRAN-ARMITAGE       |     P=0.245                                        |     P=0.491N                                       |
|FISHER EXACT           |                     P=0.250         P=0.289        |                     P=0.347         P=0.553N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE   5
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       3/49 (6%)       4/50 (8%)      |     2/48 (4%)       0/49 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      4.5%           13.1%           13.1%          |      6.3%            0.0%            0.0%          |
|TERMINAL (d)           |     1/22 (5%)       2/21 (10%)      3/27 (11%)     |     1/28 (4%)       0/30 (0%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      733 (T)         720             643           |      695             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.196         P=0.293         P=0.237        |     P=0.100N        P=0.224N        P=0.235N       |
|INCIDENTAL TUMOR       |     P=0.141         P=0.297         P=0.161        |     P=0.120N        P=0.232N        P=0.291N       |
|LOGISTIC REGRESSION    |     P=0.155         P=0.289         P=0.187        |     P=0.099N        P=0.224N        P=0.235N       |
|COCHRAN-ARMITAGE       |     P=0.137                                        |     P=0.098N                                       |
|FISHER EXACT           |                     P=0.301         P=0.181        |                     P=0.242N        P=0.237N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       4/49 (8%)       5/50 (10%)     |     3/48 (6%)       0/49 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      9.1%           17.7%           15.9%          |      9.7%            0.0%            3.3%          |
|TERMINAL (d)           |     2/22 (9%)       3/21 (14%)      3/27 (11%)     |     2/28 (7%)       0/30 (0%)       1/30 (3%)      |
|FIRST INCIDENCE (DAYS) |      733 (T)         720             643           |      695             ---             734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.255         P=0.317         P=0.296        |     P=0.178N        P=0.110N        P=0.290N       |
|INCIDENTAL TUMOR       |     P=0.186         P=0.321         P=0.204        |     P=0.202N        P=0.115N        P=0.335N       |
|LOGISTIC REGRESSION    |     P=0.200         P=0.318         P=0.230        |     P=0.181N        P=0.106N        P=0.298N       |
|COCHRAN-ARMITAGE       |     P=0.173                                        |     P=0.179N                                       |
|FISHER EXACT           |                     P=0.329         P=0.218        |                     P=0.117N        P=0.293N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE   6
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       0/50 (0%)       6/50 (12%)     |     0/50 (0%)       1/49 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |     18.2%            0.0%           20.7%          |      0.0%            2.7%            0.0%          |
|TERMINAL (d)           |     4/22 (18%)      0/21 (0%)       5/27 (19%)     |     0/29 (0%)       0/29 (0%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      733 (T)         ---             680           |      ---             700             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.352         P=0.066N        P=0.491        |     P=0.730N        P=0.517           (e)          |
|INCIDENTAL TUMOR       |     P=0.342         P=0.066N        P=0.477        |     P=0.690         P=0.500           (e)          |
|LOGISTIC REGRESSION    |     P=0.315         P=0.066N        P=0.443        |     P=0.729N        P=0.495           (e)          |
|COCHRAN-ARMITAGE       |     P=0.259                                        |     P=0.727N                                       |
|FISHER EXACT           |                     P=0.059N        P=0.370        |                     P=0.495           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     5/50 (10%)      0/50 (0%)       6/50 (12%)     |     0/50 (0%)       1/49 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |     22.7%            0.0%           20.7%          |      0.0%            2.7%            0.0%          |
|TERMINAL (d)           |     5/22 (23%)      0/21 (0%)       5/27 (19%)     |     0/29 (0%)       0/29 (0%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      733 (T)         ---             680           |      ---             700             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.517         P=0.034N*       P=0.626N       |     P=0.730N        P=0.517           (e)          |
|INCIDENTAL TUMOR       |     P=0.507         P=0.034N*       P=0.622        |     P=0.690         P=0.500           (e)          |
|LOGISTIC REGRESSION    |     P=0.477         P=0.034N*       P=0.588        |     P=0.729N        P=0.495           (e)          |
|COCHRAN-ARMITAGE       |     P=0.405                                        |     P=0.727N                                       |
|FISHER EXACT           |                     P=0.028N*       P=0.500        |                     P=0.495           (e)          |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE   7
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     5/50 (10%)      0/50 (0%)       6/50 (12%)     |     0/50 (0%)       1/49 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |     22.7%            0.0%           20.7%          |      0.0%            2.7%            0.0%          |
|TERMINAL (d)           |     5/22 (23%)      0/21 (0%)       5/27 (19%)     |     0/29 (0%)       0/29 (0%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      733 (T)         ---             680           |      ---             700             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.517         P=0.034N*       P=0.626N       |     P=0.730N        P=0.517           (e)          |
|INCIDENTAL TUMOR       |     P=0.507         P=0.034N*       P=0.622        |     P=0.690         P=0.500           (e)          |
|LOGISTIC REGRESSION    |     P=0.477         P=0.034N*       P=0.588        |     P=0.729N        P=0.495           (e)          |
|COCHRAN-ARMITAGE       |     P=0.405                                        |     P=0.727N                                       |
|FISHER EXACT           |                     P=0.028N*       P=0.500        |                     P=0.495           (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       1/50 (2%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.3%            0.0%            3.7%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/22 (0%)       0/21 (0%)       1/27 (4%)      |     0/29 (0%)       0/30 (0%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      618             ---             733 (T)       |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.350N        P=0.246N        P=0.464N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.459N        P=0.261N        P=0.615N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.372N        P=0.214N        P=0.494N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.377N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.247N        P=0.500N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE   8
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       1/50 (2%)       1/50 (2%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      5.3%            3.0%            3.7%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/22 (0%)       0/21 (0%)       1/27 (4%)      |     0/29 (0%)       0/30 (0%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      618             668             733 (T)       |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.365N        P=0.522N        P=0.464N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.472N        P=0.517N        P=0.615N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.376N        P=0.471N        P=0.494N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.386N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.500N        P=0.500N       |                       (e)             (e)          |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Sarcoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |      0.0%            0.0%            4.1%          |
|TERMINAL (d)           |     0/22 (0%)       0/21 (0%)       0/27 (0%)      |     0/29 (0%)       0/30 (0%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      ---             ---             405           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.093           (e)           P=0.235        |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.121           (e)           P=0.215        |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.300           (e)           P=0.496        |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.095                                        |
|FISHER EXACT           |                       (e)             (e)          |                       (e)           P=0.247        |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE   9
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |     3/50 (6%)       1/50 (2%)       2/50 (4%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |     10.3%            3.3%            6.7%          |
|TERMINAL (d)           |     0/22 (0%)       0/21 (0%)       0/27 (0%)      |     3/29 (10%)      1/30 (3%)       2/30 (7%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      734 (T)         734 (T)         734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.397N        P=0.292N        P=0.484N       |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.397N        P=0.292N        P=0.484N       |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.397N        P=0.292N        P=0.484N       |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.411N                                       |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.309N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |     4/50 (8%)       1/50 (2%)       2/50 (4%)      |
|ADJUSTED (b)           |      0.0%            0.0%            0.0%          |     13.8%            3.3%            6.7%          |
|TERMINAL (d)           |     0/22 (0%)       0/21 (0%)       0/27 (0%)      |     4/29 (14%)      1/30 (3%)       2/30 (7%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             ---           |      734 (T)         734 (T)         734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |       (e)             (e)             (e)          |     P=0.235N        P=0.167N        P=0.319N       |
|INCIDENTAL TUMOR       |       (e)             (e)             (e)          |     P=0.235N        P=0.167N        P=0.319N       |
|LOGISTIC REGRESSION    |       (e)             (e)             (e)          |     P=0.235N        P=0.167N        P=0.319N       |
|COCHRAN-ARMITAGE       |       (e)                                          |     P=0.249N                                       |
|FISHER EXACT           |                       (e)             (e)          |                     P=0.181N        P=0.339N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE  10
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/50 (12%)      1/50 (2%)       4/50 (8%)      |    19/50 (38%)     15/50 (30%)     17/50 (34%)     |
|ADJUSTED (b)           |     25.1%            4.8%           13.5%          |     51.8%           46.0%           46.0%          |
|TERMINAL (d)           |     5/22 (23%)      1/21 (5%)       3/27 (11%)     |    12/29 (41%)     13/30 (43%)     11/30 (37%)     |
|FIRST INCIDENCE (DAYS) |      695             733 (T)         680           |      602             572             629           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.216N        P=0.064N        P=0.263N       |     P=0.367N        P=0.223N        P=0.407N       |
|INCIDENTAL TUMOR       |     P=0.231N        P=0.061N        P=0.288N       |     P=0.395N        P=0.206N        P=0.477N       |
|LOGISTIC REGRESSION    |     P=0.251N        P=0.061N        P=0.314N       |     P=0.421N        P=0.208N        P=0.457N       |
|COCHRAN-ARMITAGE       |     P=0.299N                                       |     P=0.384N                                       |
|FISHER EXACT           |                     P=0.056N        P=0.370N       |                     P=0.263N        P=0.418N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma or Adenoma                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/50 (12%)      1/50 (2%)       4/50 (8%)      |    20/50 (40%)     15/50 (30%)     17/50 (34%)     |
|ADJUSTED (b)           |     25.1%            4.8%           13.5%          |     54.6%           46.0%           46.0%          |
|TERMINAL (d)           |     5/22 (23%)      1/21 (5%)       3/27 (11%)     |    13/29 (45%)     13/30 (43%)     11/30 (37%)     |
|FIRST INCIDENCE (DAYS) |      695             733 (T)         680           |      602             572             629           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.216N        P=0.064N        P=0.263N       |     P=0.294N        P=0.166N        P=0.335N       |
|INCIDENTAL TUMOR       |     P=0.231N        P=0.061N        P=0.288N       |     P=0.315N        P=0.151N        P=0.393N       |
|LOGISTIC REGRESSION    |     P=0.251N        P=0.061N        P=0.314N       |     P=0.342N        P=0.150N        P=0.376N       |
|COCHRAN-ARMITAGE       |     P=0.299N                                       |     P=0.308N                                       |
|FISHER EXACT           |                     P=0.056N        P=0.370N       |                     P=0.201N        P=0.339N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE  11
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     6/50 (12%)      1/50 (2%)       4/50 (8%)      |    23/50 (46%)     16/50 (32%)     18/50 (36%)     |
|ADJUSTED (b)           |     25.1%            4.8%           13.5%          |     63.1%           49.2%           48.8%          |
|TERMINAL (d)           |     5/22 (23%)      1/21 (5%)       3/27 (11%)     |    16/29 (55%)     14/30 (47%)     12/30 (40%)     |
|FIRST INCIDENCE (DAYS) |      695             733 (T)         680           |      602             572             629           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.216N        P=0.064N        P=0.263N       |     P=0.172N        P=0.083N        P=0.208N       |
|INCIDENTAL TUMOR       |     P=0.231N        P=0.061N        P=0.288N       |     P=0.180N        P=0.071N        P=0.241N       |
|LOGISTIC REGRESSION    |     P=0.251N        P=0.061N        P=0.314N       |     P=0.209N        P=0.069N        P=0.237N       |
|COCHRAN-ARMITAGE       |     P=0.299N                                       |     P=0.185N                                       |
|FISHER EXACT           |                     P=0.056N        P=0.370N       |                     P=0.109N        P=0.208N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose                                                                                                                             |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       0/45 (0%)      |     0/49 (0%)       0/50 (0%)       0/47 (0%)      |
|ADJUSTED (b)           |      4.1%            0.0%            0.0%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     0/22 (0%)       0/21 (0%)       0/26 (0%)      |     0/29 (0%)       0/30 (0%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      576             ---             ---           |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.110N        P=0.247N        P=0.252N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.205N        P=0.290N        P=0.500N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.108N        P=0.113N        P=0.540N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.111N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.247N        P=0.274N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE  12
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       6/49 (12%)      0/50 (0%)      |     1/48 (2%)       0/49 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      7.5%           26.2%            0.0%          |      3.6%            0.0%            0.0%          |
|TERMINAL (d)           |     1/22 (5%)       5/21 (24%)      0/27 (0%)      |     1/28 (4%)       0/30 (0%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      695             692             ---           |      734 (T)         ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.182N        P=0.114         P=0.208N       |     P=0.274N        P=0.486N        P=0.486N       |
|INCIDENTAL TUMOR       |     P=0.196N        P=0.125         P=0.235N       |     P=0.274N        P=0.486N        P=0.486N       |
|LOGISTIC REGRESSION    |     P=0.206N        P=0.114         P=0.231N       |     P=0.274N        P=0.486N        P=0.486N       |
|COCHRAN-ARMITAGE       |     P=0.237N                                       |     P=0.278N                                       |
|FISHER EXACT           |                     P=0.128         P=0.247N       |                     P=0.495N        P=0.490N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     9/49 (18%)      8/49 (16%)     12/49 (24%)     |    31/49 (63%)     29/49 (59%)     28/50 (56%)     |
|ADJUSTED (b)           |     31.8%           27.4%           36.9%          |     73.4%           68.1%           65.6%          |
|TERMINAL (d)           |     5/22 (23%)      4/21 (19%)      8/27 (30%)     |    18/29 (62%)     17/30 (57%)     16/30 (53%)     |
|FIRST INCIDENCE (DAYS) |      574             522             482           |      405             572             405           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.381         P=0.553N        P=0.446        |     P=0.320N        P=0.352N        P=0.346N       |
|INCIDENTAL TUMOR       |     P=0.386         P=0.429N        P=0.387        |     P=0.260N        P=0.430N        P=0.258N       |
|LOGISTIC REGRESSION    |     P=0.254         P=0.434N        P=0.303        |     P=0.273N        P=0.413N        P=0.308N       |
|COCHRAN-ARMITAGE       |     P=0.259                                        |     P=0.265N                                       |
|FISHER EXACT           |                     P=0.500N        P=0.312        |                     P=0.418N        P=0.298N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE  13
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal Cell Adenoma                                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       1/50 (2%)       2/50 (4%)      |     1/50 (2%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      0.0%            4.8%            6.5%          |      3.4%            0.0%            3.3%          |
|TERMINAL (d)           |     0/22 (0%)       1/21 (5%)       1/27 (4%)      |     1/29 (3%)       0/30 (0%)       1/30 (3%)      |
|FIRST INCIDENCE (DAYS) |      ---             733 (T)         698           |      734 (T)         ---             734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.190         P=0.491         P=0.285        |     P=0.674         P=0.493N        P=0.755N       |
|INCIDENTAL TUMOR       |     P=0.163         P=0.491         P=0.242        |     P=0.674         P=0.493N        P=0.755N       |
|LOGISTIC REGRESSION    |     P=0.160         P=0.491         P=0.244        |     P=0.674         P=0.493N        P=0.755N       |
|COCHRAN-ARMITAGE       |     P=0.145                                        |     P=0.666                                        |
|FISHER EXACT           |                     P=0.500         P=0.247        |                     P=0.500N        P=0.753N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       2/50 (4%)       8/50 (16%)     |     1/50 (2%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      2.6%            7.5%           24.3%          |      3.4%            3.3%            0.0%          |
|TERMINAL (d)           |     0/22 (0%)       1/21 (5%)       4/27 (15%)     |     1/29 (3%)       1/30 (3%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      667             662             667           |      734 (T)         734 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.013 *       P=0.460         P=0.033 *      |     P=0.326N        P=0.755N        P=0.493N       |
|INCIDENTAL TUMOR       |     P=0.006 **      P=0.507         P=0.017 *      |     P=0.326N        P=0.755N        P=0.493N       |
|LOGISTIC REGRESSION    |     P=0.006 **      P=0.503         P=0.018 *      |     P=0.326N        P=0.755N        P=0.493N       |
|COCHRAN-ARMITAGE       |     P=0.006 **                                     |     P=0.334N                                       |
|FISHER EXACT           |                     P=0.500         P=0.015 *      |                     P=0.753N        P=0.500N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE  14
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/50 (0%)       3/50 (6%)      |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      6.6%            0.0%            9.5%          |      0.0%            0.0%            3.3%          |
|TERMINAL (d)           |     0/22 (0%)       0/21 (0%)       2/27 (7%)      |     0/29 (0%)       0/30 (0%)       1/30 (3%)      |
|FIRST INCIDENCE (DAYS) |      695             ---             629           |      ---             ---             734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.443         P=0.259N        P=0.570        |     P=0.277           (e)           P=0.507        |
|INCIDENTAL TUMOR       |     P=0.320         P=0.226N        P=0.414        |     P=0.277           (e)           P=0.507        |
|LOGISTIC REGRESSION    |     P=0.379         P=0.240N        P=0.498        |     P=0.277           (e)           P=0.507        |
|COCHRAN-ARMITAGE       |     P=0.380                                        |     P=0.272                                        |
|FISHER EXACT           |                     P=0.247N        P=0.500        |                       (e)           P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Basal Cell Carcinoma, or Basal Cell Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       2/50 (4%)       3/50 (6%)      |     1/50 (2%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      0.0%            9.5%            9.4%          |      3.4%            0.0%            3.3%          |
|TERMINAL (d)           |     0/22 (0%)       2/21 (10%)      1/27 (4%)      |     1/29 (3%)       0/30 (0%)       1/30 (3%)      |
|FIRST INCIDENCE (DAYS) |      ---             733 (T)         698           |      734 (T)         ---             734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.127         P=0.227         P=0.160        |     P=0.674         P=0.493N        P=0.755N       |
|INCIDENTAL TUMOR       |     P=0.096         P=0.227         P=0.113        |     P=0.674         P=0.493N        P=0.755N       |
|LOGISTIC REGRESSION    |     P=0.095         P=0.224         P=0.122        |     P=0.674         P=0.493N        P=0.755N       |
|COCHRAN-ARMITAGE       |     P=0.085                                        |     P=0.666                                        |
|FISHER EXACT           |                     P=0.247         P=0.121        |                     P=0.500N        P=0.753N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE  15
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Trichoepithelioma, Kertatocanthoma, Squamous Cell Carcinoma,                                                                |
|     Basal Cell Carcinoma or Adenoma, Papilloma Squamous, or Papilloma                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       4/50 (8%)      14/50 (28%)     |     2/50 (4%)       1/50 (2%)       2/50 (4%)      |
|ADJUSTED (b)           |      9.0%           16.7%           39.5%          |      6.9%            3.3%            6.7%          |
|TERMINAL (d)           |     0/22 (0%)       3/21 (14%)      7/27 (26%)     |     2/29 (7%)       1/30 (3%)       2/30 (7%)      |
|FIRST INCIDENCE (DAYS) |      667             662             629           |      734 (T)         734 (T)         734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.005 **      P=0.453         P=0.014 *      |     P=0.609N        P=0.488N        P=0.684N       |
|INCIDENTAL TUMOR       |     P<0.001 **      P=0.505         P=0.002 **     |     P=0.609N        P=0.488N        P=0.684N       |
|LOGISTIC REGRESSION    |     P=0.001 **      P=0.487         P=0.004 **     |     P=0.609N        P=0.488N        P=0.684N       |
|COCHRAN-ARMITAGE       |     P=0.001 **                                     |     P=0.608                                        |
|FISHER EXACT           |                     P=0.500         P=0.003 **     |                     P=0.500N        P=0.691N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       6/50 (12%)      4/50 (8%)      |     0/50 (0%)       2/50 (4%)       0/50 (0%)      |
|ADJUSTED (b)           |     13.8%           23.9%           14.8%          |      0.0%            6.7%            0.0%          |
|TERMINAL (d)           |     2/22 (9%)       4/21 (19%)      4/27 (15%)     |     0/29 (0%)       2/30 (7%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      662             620             733 (T)       |      ---             734 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.456N        P=0.338         P=0.559N       |     P=0.651N        P=0.245           (e)          |
|INCIDENTAL TUMOR       |     P=0.531N        P=0.347         P=0.582N       |     P=0.651N        P=0.245           (e)          |
|LOGISTIC REGRESSION    |     P=0.538N        P=0.349         P=0.616N       |     P=0.651N        P=0.245           (e)          |
|COCHRAN-ARMITAGE       |     P=0.564N                                       |     P=0.658N                                       |
|FISHER EXACT           |                     P=0.370         P=0.643N       |                     P=0.247           (e)          |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE  16
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, Sarcoma,                                                                                   |
|     Neurofibroma, or Fibroma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     4/50 (8%)       8/50 (16%)      5/50 (10%)     |     0/50 (0%)       2/50 (4%)       1/50 (2%)      |
|ADJUSTED (b)           |     13.8%           28.3%           16.8%          |      0.0%            6.7%            3.3%          |
|TERMINAL (d)           |     2/22 (9%)       4/21 (19%)      4/27 (15%)     |     0/29 (0%)       2/30 (7%)       1/30 (3%)      |
|FIRST INCIDENCE (DAYS) |      662             583             643           |      ---             734 (T)         734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.557         P=0.161         P=0.587        |     P=0.385         P=0.245         P=0.507        |
|INCIDENTAL TUMOR       |     P=0.395         P=0.159         P=0.492        |     P=0.385         P=0.245         P=0.507        |
|LOGISTIC REGRESSION    |     P=0.450         P=0.172         P=0.508        |     P=0.385         P=0.245         P=0.507        |
|COCHRAN-ARMITAGE       |     P=0.451                                        |     P=0.377                                        |
|FISHER EXACT           |                     P=0.178         P=0.500        |                     P=0.247         P=0.500        |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Subcutaneous Tissue                                                                                                        |
|     Neurofibrosarcoma, Fibrosarcoma, or Sarcoma                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       2/50 (4%)       1/50 (2%)      |     0/50 (0%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      0.0%            5.8%            2.3%          |      0.0%            0.0%            3.3%          |
|TERMINAL (d)           |     0/22 (0%)       0/21 (0%)       0/27 (0%)      |     0/29 (0%)       0/30 (0%)       1/30 (3%)      |
|FIRST INCIDENCE (DAYS) |      ---             583             643           |      ---             ---             734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.395         P=0.230         P=0.514        |     P=0.277           (e)           P=0.507        |
|INCIDENTAL TUMOR       |     P=0.187         P=0.218         P=0.282        |     P=0.277           (e)           P=0.507        |
|LOGISTIC REGRESSION    |     P=0.439         P=0.270         P=0.536        |     P=0.277           (e)           P=0.507        |
|COCHRAN-ARMITAGE       |     P=0.377                                        |     P=0.272                                        |
|FISHER EXACT           |                     P=0.247         P=0.500        |                       (e)           P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE  17
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    46/49 (94%)     49/50 (98%)     44/50 (88%)     |                                                    |
|ADJUSTED (b)           |    100.0%          100.0%           97.8%          |                                                    |
|TERMINAL (d)           |    22/22 (100%)    21/21 (100%)    26/27 (96%)     |                                                    |
|FIRST INCIDENCE (DAYS) |      574             522             468           |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.126N        P=0.267         P=0.137N       |                                                    |
|INCIDENTAL TUMOR       |     P=0.151N        P=0.298         P=0.254N       |                                                    |
|LOGISTIC REGRESSION    |     P=0.302N        P=0.250         P=0.423N       |                                                    |
|COCHRAN-ARMITAGE       |     P=0.157N                                       |                                                    |
|FISHER EXACT           |                     P=0.301         P=0.254N       |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     5/50 (10%)      6/48 (13%)      1/50 (2%)      |     4/50 (8%)       3/50 (6%)       4/50 (8%)      |
|ADJUSTED (b)           |     16.7%           23.9%            3.7%          |     13.8%            9.5%           13.3%          |
|TERMINAL (d)           |     1/22 (5%)       4/21 (19%)      1/27 (4%)      |     4/29 (14%)      2/30 (7%)       4/30 (13%)     |
|FIRST INCIDENCE (DAYS) |      662             583             733 (T)       |      734 (T)         728             734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.071N        P=0.463         P=0.083N       |     P=0.563N        P=0.477N        P=0.628N       |
|INCIDENTAL TUMOR       |     P=0.107N        P=0.460         P=0.112N       |     P=0.568         P=0.484N        P=0.628N       |
|LOGISTIC REGRESSION    |     P=0.094N        P=0.462         P=0.101N       |     P=0.561N        P=0.463N        P=0.628N       |
|COCHRAN-ARMITAGE       |     P=0.096N                                       |     P=0.575                                        |
|FISHER EXACT           |                     P=0.471         P=0.102N       |                     P=0.500N        P=0.643N       |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE  18
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     3/50 (6%)       1/48 (2%)       1/50 (2%)      |     0/50 (0%)       1/50 (2%)       2/50 (4%)      |
|ADJUSTED (b)           |     10.7%            4.5%            3.7%          |      0.0%            3.3%            4.7%          |
|TERMINAL (d)           |     1/22 (5%)       0/21 (0%)       1/27 (4%)      |     0/29 (0%)       1/30 (3%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      662             729             733 (T)       |      ---             734 (T)         531           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.180N        P=0.332N        P=0.265N       |     P=0.141         P=0.507         P=0.227        |
|INCIDENTAL TUMOR       |     P=0.213N        P=0.309N        P=0.300N       |     P=0.139         P=0.507         P=0.180        |
|LOGISTIC REGRESSION    |     P=0.199N        P=0.326N        P=0.296N       |     P=0.180         P=0.507         P=0.288        |
|COCHRAN-ARMITAGE       |     P=0.210N                                       |     P=0.145                                        |
|FISHER EXACT           |                     P=0.324N        P=0.309N       |                     P=0.500         P=0.247        |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     7/50 (14%)      7/48 (15%)      2/50 (4%)      |     4/50 (8%)       4/50 (8%)       6/50 (12%)     |
|ADJUSTED (b)           |     23.9%           27.4%            7.4%          |     13.8%           12.7%           17.4%          |
|TERMINAL (d)           |     2/22 (9%)       4/21 (19%)      2/27 (7%)      |     4/29 (14%)      3/30 (10%)      4/30 (13%)     |
|FIRST INCIDENCE (DAYS) |      662             583             733 (T)       |      734 (T)         728             531           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.048N*       P=0.569         P=0.057N       |     P=0.316         P=0.621N        P=0.379        |
|INCIDENTAL TUMOR       |     P=0.077N        P=0.575         P=0.081N       |     P=0.280         P=0.628N        P=0.352        |
|LOGISTIC REGRESSION    |     P=0.065N        P=0.568         P=0.072N       |     P=0.286         P=0.610N        P=0.356        |
|COCHRAN-ARMITAGE       |     P=0.071N                                       |     P=0.302                                        |
|FISHER EXACT           |                     P=0.581         P=0.080N       |                     P=0.643N        P=0.370        |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE  19
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     2/50 (4%)       0/48 (0%)       0/50 (0%)      |     1/50 (2%)       0/50 (0%)       1/50 (2%)      |
|ADJUSTED (b)           |      9.1%            0.0%            0.0%          |      3.4%            0.0%            3.3%          |
|TERMINAL (d)           |     2/22 (9%)       0/21 (0%)       0/27 (0%)      |     1/29 (3%)       0/30 (0%)       1/30 (3%)      |
|FIRST INCIDENCE (DAYS) |      733 (T)         ---             ---           |      734 (T)         ---             734 (T)       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.086N        P=0.247N        P=0.194N       |     P=0.674         P=0.493N        P=0.755N       |
|INCIDENTAL TUMOR       |     P=0.086N        P=0.247N        P=0.194N       |     P=0.674         P=0.493N        P=0.755N       |
|LOGISTIC REGRESSION    |     P=0.086N        P=0.247N        P=0.194N       |     P=0.674         P=0.493N        P=0.755N       |
|COCHRAN-ARMITAGE       |     P=0.104N                                       |     P=0.666                                        |
|FISHER EXACT           |                     P=0.258N        P=0.247N       |                     P=0.500N        P=0.753N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     7/50 (14%)     12/50 (24%)     13/50 (26%)     |
|ADJUSTED (b)           |                                                    |     21.2%           32.9%           35.9%          |
|TERMINAL (d)           |                                                    |     4/29 (14%)      7/30 (23%)      8/30 (27%)     |
|FIRST INCIDENCE (DAYS) |                                                    |      661             643             575           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.111         P=0.196         P=0.124        |
|INCIDENTAL TUMOR       |                                                    |     P=0.059         P=0.179         P=0.072        |
|LOGISTIC REGRESSION    |                                                    |     P=0.079         P=0.179         P=0.093        |
|COCHRAN-ARMITAGE       |                                                    |     P=0.093                                        |
|FISHER EXACT           |                                                    |                     P=0.154         P=0.105        |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE  20
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |     3/50 (6%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |                                                    |      6.6%            3.3%            0.0%          |
|TERMINAL (d)           |                                                    |     0/29 (0%)       1/30 (3%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |                                                    |      531             734 (T)         ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.067N        P=0.296N        P=0.132N       |
|INCIDENTAL TUMOR       |                                                    |     P=0.083N        P=0.757N        P=0.139N       |
|LOGISTIC REGRESSION    |                                                    |     P=0.037N*       P=0.456N        P=0.060N       |
|COCHRAN-ARMITAGE       |                                                    |     P=0.063N                                       |
|FISHER EXACT           |                                                    |                     P=0.309N        P=0.121N       |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |    10/50 (20%)     13/50 (26%)     13/50 (26%)     |
|ADJUSTED (b)           |                                                    |     26.4%           35.9%           35.9%          |
|TERMINAL (d)           |                                                    |     4/29 (14%)      8/30 (27%)      8/30 (27%)     |
|FIRST INCIDENCE (DAYS) |                                                    |      531             643             575           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |     P=0.307         P=0.374         P=0.335        |
|INCIDENTAL TUMOR       |                                                    |     P=0.214         P=0.189         P=0.234        |
|LOGISTIC REGRESSION    |                                                    |     P=0.272         P=0.310         P=0.313        |
|COCHRAN-ARMITAGE       |                                                    |     P=0.284                                        |
|FISHER EXACT           |                                                    |                     P=0.318         P=0.318        |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE  21
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear,                                                                              |
|     or Undifferentiated                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    27/50 (54%)     21/50 (42%)     19/50 (38%)     |    11/50 (22%)     11/50 (22%)     10/50 (20%)     |
|ADJUSTED (b)           |     68.3%           53.1%           47.1%          |     28.2%           26.3%           25.5%          |
|TERMINAL (d)           |    11/22 (50%)      5/21 (24%)      8/27 (30%)     |     3/29 (10%)      3/30 (10%)      4/30 (13%)     |
|FIRST INCIDENCE (DAYS) |      574             559             453           |      646             575             361           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.061N        P=0.290N        P=0.065N       |     P=0.461N        P=0.536N        P=0.500N       |
|INCIDENTAL TUMOR       |     P=0.121N        P=0.193N        P=0.110N       |     P=0.519N        P=0.531N        P=0.549        |
|LOGISTIC REGRESSION    |     P=0.060N        P=0.161N        P=0.072N       |     P=0.395N        P=0.568         P=0.458N       |
|COCHRAN-ARMITAGE       |     P=0.068N                                       |     P=0.452N                                       |
|FISHER EXACT           |                     P=0.158N        P=0.080N       |                     P=0.595N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma Benign, Malignant, NOS                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     1/50 (2%)       2/50 (4%)       1/50 (2%)      |     0/50 (0%)       0/50 (0%)       0/50 (0%)      |
|ADJUSTED (b)           |      4.5%            4.0%            3.7%          |      0.0%            0.0%            0.0%          |
|TERMINAL (d)           |     1/22 (5%)       0/21 (0%)       1/27 (4%)      |     0/29 (0%)       0/30 (0%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      733 (T)         522             733 (T)       |      ---             ---             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.597N        P=0.492         P=0.716N       |       (e)             (e)             (e)          |
|INCIDENTAL TUMOR       |     P=0.229N        P=0.509N        P=0.716N       |       (e)             (e)             (e)          |
|LOGISTIC REGRESSION    |     P=0.527N        P=0.647         P=0.716N       |       (e)             (e)             (e)          |
|COCHRAN-ARMITAGE       |     P=0.620N                                       |       (e)                                          |
|FISHER EXACT           |                     P=0.500         P=0.753N       |                       (e)             (e)          |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE  22
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Osteosarcoma or Osteoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |     0/50 (0%)       0/50 (0%)       2/50 (4%)      |     1/50 (2%)       1/50 (2%)       0/50 (0%)      |
|ADJUSTED (b)           |      0.0%            0.0%            5.9%          |      2.3%            2.0%            0.0%          |
|TERMINAL (d)           |     0/22 (0%)       0/21 (0%)       0/27 (0%)      |     0/29 (0%)       0/30 (0%)       0/30 (0%)      |
|FIRST INCIDENCE (DAYS) |      ---             ---             657           |      626             569             ---           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.113           (e)           P=0.266        |     P=0.342N        P=0.748N        P=0.509N       |
|INCIDENTAL TUMOR       |     P=0.073           (e)           P=0.199        |     P=0.193N        P=0.677N        P=0.362N       |
|LOGISTIC REGRESSION    |     P=0.094           (e)           P=0.237        |     P=0.255N        P=0.647         P=0.467N       |
|COCHRAN-ARMITAGE       |     P=0.095                                        |     P=0.334N                                       |
|FISHER EXACT           |                       (e)           P=0.247        |                     P=0.753N        P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    49/50 (98%)     50/50 (100%)    48/50 (96%)     |    43/50 (86%)     41/50 (82%)     46/50 (92%)     |
|ADJUSTED (b)           |    100.0%          100.0%          100.0%          |     95.5%           93.0%           97.9%          |
|TERMINAL (d)           |    22/22 (100%)    21/21 (100%)    27/27 (100%)    |    27/29 (93%)     27/30 (90%)     29/30 (97%)     |
|FIRST INCIDENCE (DAYS) |      574             522             468           |      405             572             405           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.167N        P=0.357         P=0.181N       |     P=0.374         P=0.315N        P=0.415        |
|INCIDENTAL TUMOR       |     P=0.610         P=0.490         P=0.534        |     P=0.151         P=0.374N        P=0.217        |
|LOGISTIC REGRESSION    |     P=0.437         P=0.484         P=0.586        |     P=0.130         P=0.276N        P=0.153        |
|COCHRAN-ARMITAGE       |     P=0.355N                                       |     P=0.225                                        |
|FISHER EXACT           |                     P=0.500         P=0.500N       |                     P=0.393N        P=0.262        |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE  23
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |      UNTREATD        0.012%          0.025%        |      UNTREATD        0.012%          0.025%        |
|                       |      CONTROL                                       |      CONTROL                                       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    39/50 (78%)     33/50 (66%)     30/50 (60%)     |    21/50 (42%)     22/50 (44%)     20/50 (40%)     |
|ADJUSTED (b)           |     86.0%           69.4%           68.0%          |     47.5%           50.2%           49.1%          |
|TERMINAL (d)           |    16/22 (73%)      7/21 (33%)     14/27 (52%)     |     7/29 (24%)     10/30 (33%)     11/30 (37%)     |
|FIRST INCIDENCE (DAYS) |      574             522             453           |      531             569             361           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.054N        P=0.352N        P=0.049N*      |     P=0.465N        P=0.564         P=0.497N       |
|INCIDENTAL TUMOR       |     P=0.059N        P=0.089N        P=0.063N       |     P=0.455N        P=0.473         P=0.578N       |
|LOGISTIC REGRESSION    |     P=0.075N        P=0.097N        P=0.078N       |     P=0.387N        P=0.468         P=0.438N       |
|COCHRAN-ARMITAGE       |     P=0.035N*                                      |     P=0.458N                                       |
|FISHER EXACT           |                     P=0.133N        P=0.041N*      |                     P=0.500         P=0.500N       |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |       #               #               #            |       #               #               #            |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |    50/50 (100%)    50/50 (100%)    49/50 (98%)     |    48/50 (96%)     47/50 (94%)     49/50 (98%)     |
|ADJUSTED (b)           |    100.0%          100.0%          100.0%          |     98.0%           95.9%           98.0%          |
|TERMINAL (d)           |    22/22 (100%)    21/21 (100%)    27/27 (100%)    |    28/29 (97%)     28/30 (93%)     29/30 (97%)     |
|FIRST INCIDENCE (DAYS) |      574             522             453           |      405             569             361           |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |     P=0.171N        P=0.405         P=0.188N       |     P=0.501         P=0.372N        P=0.533        |
|INCIDENTAL TUMOR       |     P=0.638N          (e)             (e)          |     P=0.375         P=0.545N        P=0.414        |
|LOGISTIC REGRESSION    |     P=0.638N          (e)             (e)          |     P=0.404         P=0.508N        P=0.501        |
|COCHRAN-ARMITAGE       |     P=0.272N                                       |     P=0.395                                        |
|FISHER EXACT           |                     P=1.000N        P=0.500N       |                     P=0.500N        P=0.500        |
|=================================================================================================================================|
 
         DATE: 09/07/94                     EXPERIMENT: 05048 TEST: 01                                                 PAGE  24
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- RHODAMINE 6G
 
                                                 TERMINAL SACRIFICE AT 105 WEEKS
 
 
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (d)  Observed incidence at terminal kill.
 (f)  Beneath the control incidence are the P-values associated with the trend 
      test.  Beneath the dosed group incidence are the P-values corresponding to 
      pairwise comparisons between the controls and that dosed group.  The life
      table analysis regards tumors in animals dying  prior to terminal kill as
      being (directly or indirectly) the cause of death.  The incidental tumor 
      test regards these lesions as non-fatal.  Logistic regression is an alternative
      method for analyzing the incidence of non-fatal tumors.  The Cochran-Armitage
      and Fisher's exact tests compare directly the overall incidence rates.  
      For all tests, a negative trend is indicated by "N".
 (e)  Value of Statistic cannot be computed. 
 (I)  Interim sacrifice
 (T)  Terminal sacrifice
  #   Tumor rates based on number of animals necropsied.
 
  *   To the right of any statistical result, indicates significance at (P<=0.05).
  **  To the right of any statistical result, indicates significance at (P<=0.01).