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TDMS Study 05122-05 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: LITRI                                             NICKEL SULFATE HEXAHYDRATE                              DATE: 05/20/95       
EXPERIMENT: 05122 TEST: 05                                                                                     TIME: 03:19:03       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: Y01-ES-30108                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C60344       
PATHOLOGIST: K. NIKULA                                                                                         CAS: 010101970       
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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: LITRI                                             NICKEL SULFATE HEXAHYDRATE                              DATE: 05/20/95       
EXPERIMENT: 05122 TEST: 05                                                                                     TIME: 03:19:03       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: Y01-ES-30108                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C60344       
PATHOLOGIST: K. NIKULA                                                                                         CAS: 010101970       


                                                    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 Cortex
                                                    Adrenal Medulla
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Clitoral/Preputial Gland
                                                    Epididymis
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Larynx
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: LITRI                                             NICKEL SULFATE HEXAHYDRATE                              DATE: 05/20/95       
EXPERIMENT: 05122 TEST: 05                                                                                     TIME: 03:19:03       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: Y01-ES-30108                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C60344       
PATHOLOGIST: K. NIKULA                                                                                         CAS: 010101970       


                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                   IN THE ANALYSIS OF THE STUDY OF NICKEL SULFATE HEXAHYDRATE
              ====================================================================================================
                                                           MALE RATS
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------
              Adrenal Medulla               Pheochromocytoma Benign
                                            Pheochromocytoma: Benign, Complex, Malignant, NOS
              Lung                          Alveolar/Bronchiolar Adenoma
              Skin                          Fibroma
                                            Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, or Fibrous Histiocytoma
                                            Keratoacanthoma
              Thyroid Gland: C-Cell         Adenoma
                                            Carcinoma or Adenoma
              All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated
              ====================================================================================================
                                                           FEMALE RATS
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------
              Mammary Gland                 Carcinoma
                                            Carcinoma or Adenoma
                                            Fibroadenoma
                                            Fibroma, Fibroadenoma or Adenoma
                                            Fibroma, Fibroadenoma, Carcinoma, or Adenoma
              All Organs                    Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated
                                            Benign Tumors
                                            Malignant and Benign Tumors
              ====================================================================================================
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE   1
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 16/59 (27%)  16/58 (28%)  12/58 (21%)  11/58 (19%) |  2/56 (4%)    4/57 (7%)    2/58 (3%)    3/59 (5%)  |
|ADJUSTED (b)           |  61.2%        62.3%        46.2%        43.3%      |   6.6%        15.5%         6.8%        10.3%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/4 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  7/16 (44%)   8/16 (50%)   6/18 (33%)   7/21 (33%) |  1/22 (5%)    1/17 (6%)    1/28 (4%)    3/29 (10%) |
|FIRST INCIDENCE (DAYS) |   622          580          471          688       |   584          644          711          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.045N*    P=0.523N     P=0.185N     P=0.088N   |  P=0.516N     P=0.238      P=0.628N     P=0.583    |
|INCIDENTAL TUMOR       |  P=0.101N     P=0.464N     P=0.246N     P=0.178N   |  P=0.463      P=0.362      P=0.681N     P=0.483    |
|LOGISTIC REGRESSION    |  P=0.083N     P=0.475N     P=0.201N     P=0.142N   |  P=0.535      P=0.317      P=0.671N     P=0.486    |
|COCHRAN-ARMITAGE       |  P=0.128N                                          |  P=0.551                                           |
|FISHER EXACT           |               P=0.560      P=0.275N     P=0.204N   |               P=0.348      P=0.677N     P=0.525    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Malignant                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/59 (0%)    3/58 (5%)    2/58 (3%)    1/58 (2%)  |  0/56 (0%)    0/57 (0%)    0/58 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   0.0%         9.7%         8.5%         4.8%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/4 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    1/18 (6%)    1/21 (5%)  |  0/22 (0%)    0/17 (0%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          632          651          733 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.601      P=0.150      P=0.253      P=0.554    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.527      P=0.152      P=0.238      P=0.554    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.568      P=0.126      P=0.246      P=0.554    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.557                                           |    (e)                                             |
|FISHER EXACT           |               P=0.119      P=0.244      P=0.496    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE   2
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 16/59 (27%)  19/58 (33%)  13/58 (22%)  12/58 (21%) |  2/56 (4%)    4/57 (7%)    3/58 (5%)    3/59 (5%)  |
|ADJUSTED (b)           |  61.2%        66.0%        50.7%        47.4%      |   6.6%        15.5%         9.6%        10.3%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/4 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  7/16 (44%)   8/16 (50%)   7/18 (39%)   8/21 (38%) |  1/22 (5%)    1/17 (6%)    1/28 (4%)    3/29 (10%) |
|FIRST INCIDENCE (DAYS) |   622          580          471          688       |   584          644          700          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.049N*    P=0.419      P=0.243N     P=0.122N   |  P=0.524N     P=0.238      P=0.584      P=0.583    |
|INCIDENTAL TUMOR       |  P=0.112N     P=0.469      P=0.321N     P=0.241N   |  P=0.423      P=0.362      P=0.518      P=0.483    |
|LOGISTIC REGRESSION    |  P=0.091N     P=0.442      P=0.270N     P=0.167N   |  P=0.514      P=0.317      P=0.532      P=0.486    |
|COCHRAN-ARMITAGE       |  P=0.140N                                          |  P=0.530                                           |
|FISHER EXACT           |               P=0.321      P=0.354N     P=0.275N   |               P=0.348      P=0.517      P=0.525    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/59 (3%)    0/58 (0%)    3/57 (5%)    3/58 (5%)  |  4/56 (7%)    4/57 (7%)    3/57 (5%)    3/59 (5%)  |
|ADJUSTED (b)           |   7.8%         0.0%         9.9%         8.9%      |  13.9%        19.7%         9.2%        10.3%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    1/17 (6%)    1/21 (5%)  |  1/22 (5%)    3/17 (18%)   2/28 (7%)    3/29 (10%) |
|FIRST INCIDENCE (DAYS) |   622          ---          538          460       |   683          596          647          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.266      P=0.231N     P=0.513      P=0.543    |  P=0.242N     P=0.471      P=0.413N     P=0.405N   |
|INCIDENTAL TUMOR       |  P=0.251      P=0.206N     P=0.493      P=0.487    |  P=0.359N     P=0.558      P=0.444N     P=0.546N   |
|LOGISTIC REGRESSION    |  P=0.220      P=0.230N     P=0.485      P=0.489    |  P=0.353N     P=0.532      P=0.460N     P=0.497N   |
|COCHRAN-ARMITAGE       |  P=0.223                                           |  P=0.362N                                          |
|FISHER EXACT           |               P=0.252N     P=0.484      P=0.492    |               P=0.632N     P=0.490N     P=0.471N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE   3
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/59 (2%)    3/58 (5%)    1/57 (2%)    1/58 (2%)  |  0/56 (0%)    1/57 (2%)    0/57 (0%)    1/59 (2%)  |
|ADJUSTED (b)           |   1.9%         8.0%         3.2%         2.2%      |   0.0%         3.4%         0.0%         3.4%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    0/17 (0%)    0/21 (0%)  |  0/22 (0%)    0/17 (0%)    0/28 (0%)    1/29 (3%)  |
|FIRST INCIDENCE (DAYS) |   482          607          679          563       |   ---          653          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.447N     P=0.333      P=0.750N     P=0.756    |  P=0.459      P=0.446        (e)        P=0.555    |
|INCIDENTAL TUMOR       |  P=0.472N     P=0.203      P=0.728      P=0.741    |  P=0.404      P=0.443        (e)        P=0.555    |
|LOGISTIC REGRESSION    |  P=0.451N     P=0.274      P=0.744      P=0.728    |  P=0.412      P=0.500        (e)        P=0.555    |
|COCHRAN-ARMITAGE       |  P=0.444N                                          |  P=0.420                                           |
|FISHER EXACT           |               P=0.303      P=0.743      P=0.748    |               P=0.504        (e)        P=0.513    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/59 (5%)    3/58 (5%)    4/57 (7%)    4/58 (7%)  |  4/56 (7%)    5/57 (9%)    3/57 (5%)    4/59 (7%)  |
|ADJUSTED (b)           |   9.6%         8.0%        12.8%        10.9%      |  13.9%        22.4%         9.2%        13.8%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    1/17 (6%)    1/21 (5%)  |  1/22 (5%)    3/17 (18%)   2/28 (7%)    4/29 (14%) |
|FIRST INCIDENCE (DAYS) |   482          607          538          460       |   683          596          647          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.418      P=0.632N     P=0.518      P=0.534    |  P=0.327N     P=0.323      P=0.413N     P=0.535N   |
|INCIDENTAL TUMOR       |  P=0.385      P=0.611      P=0.472      P=0.474    |  P=0.472N     P=0.395      P=0.444N     P=0.625    |
|LOGISTIC REGRESSION    |  P=0.373      P=0.645      P=0.476      P=0.471    |  P=0.465N     P=0.393      P=0.460N     P=0.638N   |
|COCHRAN-ARMITAGE       |  P=0.381                                           |  P=0.467N                                          |
|FISHER EXACT           |               P=0.652      P=0.481      P=0.490    |               P=0.511      P=0.490N     P=0.612N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE   4
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/57 (4%)    2/56 (4%)    1/57 (2%)    4/58 (7%)  |  0/57 (0%)    0/58 (0%)    0/58 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   6.8%         6.1%         5.9%        14.9%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     1/5 (20%)    0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    1/17 (6%)    2/21 (10%) |  0/22 (0%)    0/17 (0%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   657          458 (I)      733 (T)      630       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.266      P=0.666N     P=0.477N     P=0.384    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.203      P=0.663N     P=0.524N     P=0.309    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.235      P=0.679      P=0.493N     P=0.355    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.237                                           |    (e)                                             |
|FISHER EXACT           |               P=0.684      P=0.500N     P=0.348    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/57 (4%)    2/56 (4%)    2/57 (4%)    5/58 (9%)  |  0/57 (0%)    0/58 (0%)    0/58 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   6.8%         6.1%         8.4%        17.4%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     1/5 (20%)    0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    1/17 (6%)    2/21 (10%) |  0/22 (0%)    0/17 (0%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   657          458 (I)      614          630       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.141      P=0.666N     P=0.679N     P=0.261    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.107      P=0.663N     P=0.689      P=0.209    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.120      P=0.679      P=0.692N     P=0.231    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.121                                           |    (e)                                             |
|FISHER EXACT           |               P=0.684      P=0.691N     P=0.226    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE   5
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/59 (2%)    0/58 (0%)    2/58 (3%)    2/58 (3%)  |  0/57 (0%)    0/58 (0%)    0/58 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   3.2%         0.0%         6.0%         5.2%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    0/18 (0%)    0/21 (0%)  |  0/22 (0%)    0/17 (0%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   657          ---          471          583       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.244      P=0.488N     P=0.519      P=0.508    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.206      P=0.466N     P=0.451      P=0.490    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.235      P=0.497N     P=0.488      P=0.493    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.238                                           |    (e)                                             |
|FISHER EXACT           |               P=0.504N     P=0.494      P=0.494    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/59 (3%)    1/58 (2%)    2/58 (3%)    2/58 (3%)  |  0/57 (0%)    0/58 (0%)    0/58 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   5.6%         6.3%         6.0%         5.2%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    1/16 (6%)    0/18 (0%)    0/21 (0%)  |  0/22 (0%)    0/17 (0%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   610          733 (T)      471          583       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.540      P=0.490N     P=0.684N     P=0.685N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.508      P=0.464N     P=0.662      P=0.692N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.516      P=0.490N     P=0.682      P=0.686    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.517                                           |    (e)                                             |
|FISHER EXACT           |               P=0.506N     P=0.684      P=0.684    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE   6
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/59 (3%)    1/58 (2%)    2/58 (3%)    2/58 (3%)  |  0/57 (0%)    0/58 (0%)    0/58 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   5.6%         6.3%         6.0%         5.2%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    1/16 (6%)    0/18 (0%)    0/21 (0%)  |  0/22 (0%)    0/17 (0%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   610          733 (T)      471          583       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.540      P=0.490N     P=0.684N     P=0.685N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.508      P=0.464N     P=0.662      P=0.692N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.516      P=0.490N     P=0.682      P=0.686    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.517                                           |    (e)                                             |
|FISHER EXACT           |               P=0.506N     P=0.684      P=0.684    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/64 (0%)    0/63 (0%)    0/63 (0%)    2/63 (3%)  |  0/62 (0%)    0/63 (0%)    0/63 (0%)    1/64 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         9.5%      |   0.0%         0.0%         0.0%         3.4%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    0/18 (0%)    2/21 (10%) |  0/22 (0%)    0/17 (0%)    0/28 (0%)    1/29 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          733 (T)   |   ---          ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.068        (e)          (e)        P=0.299    |  P=0.247        (e)          (e)        P=0.555    |
|INCIDENTAL TUMOR       |  P=0.068        (e)          (e)        P=0.299    |  P=0.247        (e)          (e)        P=0.555    |
|LOGISTIC REGRESSION    |  P=0.068        (e)          (e)        P=0.299    |  P=0.247        (e)          (e)        P=0.555    |
|COCHRAN-ARMITAGE       |  P=0.046 *                                         |  P=0.201                                           |
|FISHER EXACT           |                 (e)          (e)        P=0.244    |                 (e)          (e)        P=0.508    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE   7
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/64 (2%)    0/63 (0%)    1/63 (2%)    3/63 (5%)  |  0/62 (0%)    0/63 (0%)    0/63 (0%)    1/64 (2%)  |
|ADJUSTED (b)           |   6.3%         0.0%         4.0%        11.8%      |   0.0%         0.0%         0.0%         3.4%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  1/16 (6%)    0/16 (0%)    0/18 (0%)    2/21 (10%) |  0/22 (0%)    0/17 (0%)    0/28 (0%)    1/29 (3%)  |
|FIRST INCIDENCE (DAYS) |   733 (T)      ---          711          628       |   ---          ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.137      P=0.500N     P=0.722N     P=0.396    |  P=0.247        (e)          (e)        P=0.555    |
|INCIDENTAL TUMOR       |  P=0.114      P=0.500N     P=0.759      P=0.394    |  P=0.247        (e)          (e)        P=0.555    |
|LOGISTIC REGRESSION    |  P=0.099      P=0.500N     P=0.740N     P=0.326    |  P=0.247        (e)          (e)        P=0.555    |
|COCHRAN-ARMITAGE       |  P=0.094                                           |  P=0.201                                           |
|FISHER EXACT           |               P=0.504N     P=0.748      P=0.304    |                 (e)          (e)        P=0.508    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/64 (2%)    1/63 (2%)    0/63 (0%)    0/63 (0%)  |  4/63 (6%)    4/63 (6%)    1/63 (2%)    1/64 (2%)  |
|ADJUSTED (b)           |   6.3%         6.3%         0.0%         0.0%      |  13.9%        21.1%         2.5%         3.4%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  1/16 (6%)    1/16 (6%)    0/18 (0%)    0/21 (0%)  |  2/22 (9%)    2/17 (12%)   0/28 (0%)    1/29 (3%)  |
|FIRST INCIDENCE (DAYS) |   733 (T)      733 (T)      ---          ---       |   643          706          662          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.193N     P=0.764      P=0.477N     P=0.446N   |  P=0.044N*    P=0.482      P=0.147N     P=0.141N   |
|INCIDENTAL TUMOR       |  P=0.193N     P=0.764      P=0.477N     P=0.446N   |  P=0.083N     P=0.555      P=0.175N     P=0.240N   |
|LOGISTIC REGRESSION    |  P=0.193N     P=0.764      P=0.477N     P=0.446N   |  P=0.065N     P=0.499      P=0.164N     P=0.191N   |
|COCHRAN-ARMITAGE       |  P=0.236N                                          |  P=0.075N                                          |
|FISHER EXACT           |               P=0.748      P=0.504N     P=0.504N   |               P=0.641N     P=0.182N     P=0.178N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE   8
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/64 (2%)    1/63 (2%)    0/63 (0%)    0/63 (0%)  |  5/63 (8%)    4/63 (6%)    1/63 (2%)    1/64 (2%)  |
|ADJUSTED (b)           |   6.3%         6.3%         0.0%         0.0%      |  16.3%        21.1%         2.5%         3.4%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  1/16 (6%)    1/16 (6%)    0/18 (0%)    0/21 (0%)  |  2/22 (9%)    2/17 (12%)   0/28 (0%)    1/29 (3%)  |
|FIRST INCIDENCE (DAYS) |   733 (T)      733 (T)      ---          ---       |   643          706          662          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.193N     P=0.764      P=0.477N     P=0.446N   |  P=0.023N*    P=0.589      P=0.085N     P=0.084N   |
|INCIDENTAL TUMOR       |  P=0.193N     P=0.764      P=0.477N     P=0.446N   |  P=0.048N*    P=0.608N     P=0.098N     P=0.168N   |
|LOGISTIC REGRESSION    |  P=0.193N     P=0.764      P=0.477N     P=0.446N   |  P=0.036N*    P=0.638      P=0.093N     P=0.114N   |
|COCHRAN-ARMITAGE       |  P=0.236N                                          |  P=0.041N*                                         |
|FISHER EXACT           |               P=0.748      P=0.504N     P=0.504N   |               P=0.500N     P=0.104N     P=0.100N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/64 (0%)    1/63 (2%)    1/63 (2%)    1/63 (2%)  | 17/63 (27%)  18/63 (29%)  10/63 (16%)   9/64 (14%) |
|ADJUSTED (b)           |   0.0%         3.2%         5.6%         2.4%      |  49.0%        44.0%        28.8%        26.8%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    1/18 (6%)    0/21 (0%)  |  7/22 (32%)   1/17 (6%)    6/28 (21%)   6/29 (21%) |
|FIRST INCIDENCE (DAYS) |   ---          679          733 (T)      602       |   542          392          617          538       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.413      P=0.528      P=0.523      P=0.505    |  P=0.010N*    P=0.262      P=0.045N*    P=0.036N*  |
|INCIDENTAL TUMOR       |  P=0.383      P=0.534      P=0.523      P=0.529    |  P=0.035N*    P=0.581      P=0.086N     P=0.100N   |
|LOGISTIC REGRESSION    |  P=0.387      P=0.510      P=0.523      P=0.497    |  P=0.057N     P=0.449      P=0.067N     P=0.079N   |
|COCHRAN-ARMITAGE       |  P=0.383                                           |  P=0.019N*                                         |
|FISHER EXACT           |               P=0.496      P=0.496      P=0.496    |               P=0.500      P=0.096N     P=0.056N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE   9
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma or Adenoma                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/64 (0%)    1/63 (2%)    1/63 (2%)    1/63 (2%)  | 18/63 (29%)  18/63 (29%)  10/63 (16%)   9/64 (14%) |
|ADJUSTED (b)           |   0.0%         3.2%         5.6%         2.4%      |  50.5%        44.0%        28.8%        26.8%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    1/18 (6%)    0/21 (0%)  |  7/22 (32%)   1/17 (6%)    6/28 (21%)   6/29 (21%) |
|FIRST INCIDENCE (DAYS) |   ---          679          733 (T)      602       |   542          392          617          538       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.413      P=0.528      P=0.523      P=0.505    |  P=0.007N**   P=0.311      P=0.031N*    P=0.025N*  |
|INCIDENTAL TUMOR       |  P=0.383      P=0.534      P=0.523      P=0.529    |  P=0.024N*    P=0.515N     P=0.058N     P=0.076N   |
|LOGISTIC REGRESSION    |  P=0.387      P=0.510      P=0.523      P=0.497    |  P=0.042N*    P=0.526      P=0.044N*    P=0.053N   |
|COCHRAN-ARMITAGE       |  P=0.383                                           |  P=0.012N*                                         |
|FISHER EXACT           |               P=0.496      P=0.496      P=0.496    |               P=0.578N     P=0.066N     P=0.037N*  |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/64 (2%)    2/63 (3%)    1/63 (2%)    1/63 (2%)  | 22/63 (35%)  21/63 (33%)  11/63 (17%)  10/64 (16%) |
|ADJUSTED (b)           |   6.3%         9.3%         5.6%         2.4%      |  59.4%        53.6%        30.7%        30.0%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  1/16 (6%)    1/16 (6%)    1/18 (6%)    0/21 (0%)  |  9/22 (41%)   3/17 (18%)   6/28 (21%)   7/29 (24%) |
|FIRST INCIDENCE (DAYS) |   733 (T)      679          733 (T)      602       |   542          392          617          538       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.466N     P=0.516      P=0.737N     P=0.728N   |  P=0.001N**   P=0.322      P=0.009N**   P=0.006N** |
|INCIDENTAL TUMOR       |  P=0.488N     P=0.520      P=0.737N     P=0.714N   |  P=0.005N**   P=0.474N     P=0.016N*    P=0.028N*  |
|LOGISTIC REGRESSION    |  P=0.518N     P=0.529      P=0.737N     P=0.759N   |  P=0.010N**   P=0.568      P=0.012N*    P=0.016N*  |
|COCHRAN-ARMITAGE       |  P=0.531N                                          |  P=0.003N**                                        |
|FISHER EXACT           |               P=0.494      P=0.748      P=0.748    |               P=0.500N     P=0.021N*    P=0.010N*  |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE  10
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery                                                                                                                        |
|     Lipoma                                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/64 (0%)    2/63 (3%)    0/63 (0%)    0/63 (0%)  |  0/63 (0%)    0/63 (0%)    1/63 (2%)    0/64 (0%)  |
|ADJUSTED (b)           |   0.0%         5.7%         0.0%         0.0%      |   0.0%         0.0%         3.6%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    0/18 (0%)    0/21 (0%)  |  0/22 (0%)    0/17 (0%)    1/28 (4%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          566          ---          ---       |   ---          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.384N     P=0.261        (e)          (e)      |  P=0.736        (e)        P=0.548        (e)      |
|INCIDENTAL TUMOR       |  P=0.426N     P=0.275        (e)          (e)      |  P=0.736        (e)        P=0.548        (e)      |
|LOGISTIC REGRESSION    |  P=0.396N     P=0.238        (e)          (e)      |  P=0.736        (e)        P=0.548        (e)      |
|COCHRAN-ARMITAGE       |  P=0.397N                                          |  P=0.693                                           |
|FISHER EXACT           |               P=0.244        (e)          (e)      |                 (e)        P=0.500        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva)                                                                       |
|     Papilloma Squamous or Papilloma                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/64 (3%)    1/63 (2%)    1/63 (2%)    0/63 (0%)  |  0/63 (0%)    1/63 (2%)    0/63 (0%)    0/64 (0%)  |
|ADJUSTED (b)           |   7.3%         2.6%         2.8%         0.0%      |   0.0%         5.9%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    0/18 (0%)    0/21 (0%)  |  0/22 (0%)    1/17 (6%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   577          640          617          ---       |   ---          729 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.151N     P=0.464N     P=0.495N     P=0.224N   |  P=0.500N     P=0.449        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.154N     P=0.447N     P=0.498N     P=0.263N   |  P=0.500N     P=0.449        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.155N     P=0.494N     P=0.500N     P=0.236N   |  P=0.500N     P=0.449        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.157N                                          |  P=0.557N                                          |
|FISHER EXACT           |               P=0.506N     P=0.506N     P=0.252N   |               P=0.500        (e)          (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE  11
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva)                                                                       |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/64 (0%)    1/63 (2%)    3/63 (5%)    0/63 (0%)  |  3/63 (5%)    1/63 (2%)    2/63 (3%)    1/64 (2%)  |
|ADJUSTED (b)           |   0.0%         2.9%        13.4%         0.0%      |   6.4%         2.1%         5.1%         2.1%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    1/18 (6%)    0/21 (0%)  |  0/22 (0%)    0/17 (0%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          646          697          ---       |   536          559          661          480       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.590N     P=0.518      P=0.151        (e)      |  P=0.298N     P=0.338N     P=0.468N     P=0.355N   |
|INCIDENTAL TUMOR       |  P=0.565      P=0.534      P=0.112        (e)      |  P=0.431N     P=0.152N     P=0.659N     P=0.419N   |
|LOGISTIC REGRESSION    |  P=0.625N     P=0.504      P=0.135        (e)      |  P=0.448N     P=0.297N     P=0.623N     P=0.280N   |
|COCHRAN-ARMITAGE       |  P=0.629                                           |  P=0.278N                                          |
|FISHER EXACT           |               P=0.496      P=0.119        (e)      |               P=0.309N     P=0.500N     P=0.304N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Cavity (Oral Mucosa, Tongue, Pharynx, Tooth, Gingiva)                                                                       |
|     Squamous Cell Carcinoma, Papilloma Squamous, or Papilloma                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/64 (3%)    2/63 (3%)    4/63 (6%)    0/63 (0%)  |  3/63 (5%)    2/63 (3%)    2/63 (3%)    1/64 (2%)  |
|ADJUSTED (b)           |   7.3%         5.3%        15.8%         0.0%      |   6.4%         7.9%         5.1%         2.1%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    1/18 (6%)    0/21 (0%)  |  0/22 (0%)    1/17 (6%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   577          640          617          ---       |   536          559          661          480       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.211N     P=0.655N     P=0.377      P=0.224N   |  P=0.232N     P=0.552N     P=0.468N     P=0.355N   |
|INCIDENTAL TUMOR       |  P=0.274N     P=0.637N     P=0.327      P=0.263N   |  P=0.335N     P=0.353N     P=0.659N     P=0.419N   |
|LOGISTIC REGRESSION    |  P=0.231N     P=0.688N     P=0.348      P=0.236N   |  P=0.229N     P=0.500N     P=0.623N     P=0.280N   |
|COCHRAN-ARMITAGE       |  P=0.238N                                          |  P=0.229N                                          |
|FISHER EXACT           |               P=0.685      P=0.332      P=0.252N   |               P=0.500N     P=0.500N     P=0.304N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE  12
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Mucosa                                                                                                                      |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/64 (0%)    0/63 (0%)    3/63 (5%)    0/63 (0%)  |  3/63 (5%)    1/63 (2%)    2/63 (3%)    1/64 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%        13.4%         0.0%      |   6.4%         2.1%         5.1%         2.1%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    1/18 (6%)    0/21 (0%)  |  0/22 (0%)    0/17 (0%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          697          ---       |   536          559          661          480       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.586        (e)        P=0.151        (e)      |  P=0.298N     P=0.338N     P=0.468N     P=0.355N   |
|INCIDENTAL TUMOR       |  P=0.486        (e)        P=0.112        (e)      |  P=0.431N     P=0.152N     P=0.659N     P=0.419N   |
|LOGISTIC REGRESSION    |  P=0.553        (e)        P=0.135        (e)      |  P=0.448N     P=0.297N     P=0.623N     P=0.280N   |
|COCHRAN-ARMITAGE       |  P=0.531                                           |  P=0.278N                                          |
|FISHER EXACT           |                 (e)        P=0.119        (e)      |               P=0.309N     P=0.500N     P=0.304N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Mucosa                                                                                                                      |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/64 (3%)    1/63 (2%)    1/63 (2%)    0/63 (0%)  |  0/63 (0%)    1/63 (2%)    0/63 (0%)    0/64 (0%)  |
|ADJUSTED (b)           |   7.3%         2.6%         2.8%         0.0%      |   0.0%         5.9%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    0/18 (0%)    0/21 (0%)  |  0/22 (0%)    1/17 (6%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   577          640          617          ---       |   ---          729 (T)      ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.151N     P=0.464N     P=0.495N     P=0.224N   |  P=0.500N     P=0.449        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.154N     P=0.447N     P=0.498N     P=0.263N   |  P=0.500N     P=0.449        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.155N     P=0.494N     P=0.500N     P=0.236N   |  P=0.500N     P=0.449        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.157N                                          |  P=0.557N                                          |
|FISHER EXACT           |               P=0.506N     P=0.506N     P=0.252N   |               P=0.500        (e)          (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE  13
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 15/59 (25%)  12/56 (21%)  18/58 (31%)  14/58 (24%) | 22/57 (39%)  24/58 (41%)  24/58 (41%)  22/59 (37%) |
|ADJUSTED (b)           |  44.5%        42.4%        59.1%        46.2%      |  63.6%        72.3%        62.1%        62.3%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  2/5 (40%)    0/5 (0%)     0/5 (0%)     1/5 (20%)  |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  3/16 (19%)   3/15 (20%)   8/18 (44%)   6/21 (29%) | 11/22 (50%)   9/17 (53%)  14/28 (50%)  16/29 (55%) |
|FIRST INCIDENCE (DAYS) |   458 (I)      547          432          458 (I)   |   621          537          629          538       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.407N     P=0.304N     P=0.435      P=0.366N   |  P=0.142N     P=0.118      P=0.430N     P=0.321N   |
|INCIDENTAL TUMOR       |  P=0.481      P=0.371N     P=0.334      P=0.552N   |  P=0.454      P=0.340      P=0.561N     P=0.391    |
|LOGISTIC REGRESSION    |  P=0.523      P=0.357N     P=0.340      P=0.494N   |  P=0.522N     P=0.228      P=0.565      P=0.471    |
|COCHRAN-ARMITAGE       |  P=0.504                                           |  P=0.442N                                          |
|FISHER EXACT           |               P=0.388N     P=0.320      P=0.521N   |               P=0.455      P=0.455      P=0.518N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal Cell Carcinoma, Basal Cell Adenoma, Basosquamous Tumor (benign,                                                       |
|     malignant or NOS), or Trichoepithelioma                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/64 (0%)    1/63 (2%)    0/63 (0%)    2/63 (3%)  |  0/63 (0%)    0/63 (0%)    0/63 (0%)    0/64 (0%)  |
|ADJUSTED (b)           |   0.0%         3.4%         0.0%         6.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    0/18 (0%)    0/21 (0%)  |  0/22 (0%)    0/17 (0%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          683          ---          419       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.153      P=0.530        (e)        P=0.255    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.099      P=0.534        (e)        P=0.166    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.140      P=0.511        (e)        P=0.232    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.140                                           |    (e)                                             |
|FISHER EXACT           |               P=0.496        (e)        P=0.244    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE  14
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal or Sq. Cell Carcinoma, Carcinoma, Basosq. Tumor (M or B), Basal                                                       |
|     Cell Adenoma, Adenoma, Papilloma, Sq Papilloma, Keratoacanthoma, Trichoepithelioma                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/64 (8%)    3/63 (5%)    3/63 (5%)    4/63 (6%)  |  1/63 (2%)    0/63 (0%)    0/63 (0%)    0/64 (0%)  |
|ADJUSTED (b)           |  18.7%        13.4%        14.3%        15.0%      |   2.1%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  1/5 (20%)    0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  1/16 (6%)    1/16 (6%)    2/18 (11%)   2/21 (10%) |  0/22 (0%)    0/17 (0%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   458 (I)      683          685          419       |   566          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.396N     P=0.331N     P=0.305N     P=0.429N   |  P=0.323N     P=0.513N     P=0.488N     P=0.536N   |
|INCIDENTAL TUMOR       |  P=0.532N     P=0.299N     P=0.369N     P=0.570N   |  P=0.486N     P=0.372N     P=0.602N     P=0.814N   |
|LOGISTIC REGRESSION    |  P=0.479N     P=0.333N     P=0.343N     P=0.496N   |  P=0.301N     P=0.494N     P=0.504N     P=0.487N   |
|COCHRAN-ARMITAGE       |  P=0.492N                                          |  P=0.307N                                          |
|FISHER EXACT           |               P=0.368N     P=0.368N     P=0.510N   |               P=0.500N     P=0.500N     P=0.496N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/64 (0%)    1/63 (2%)    0/63 (0%)    3/63 (5%)  |  0/63 (0%)    0/63 (0%)    1/63 (2%)    2/64 (3%)  |
|ADJUSTED (b)           |   0.0%         4.3%         0.0%        10.5%      |   0.0%         0.0%         3.6%         5.5%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    0/18 (0%)    1/21 (5%)  |  0/22 (0%)    0/17 (0%)    1/28 (4%)    1/29 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          704          ---          628       |   ---          ---          729 (T)      480       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.060      P=0.518        (e)        P=0.161    |  P=0.095        (e)        P=0.548      P=0.258    |
|INCIDENTAL TUMOR       |  P=0.034 *    P=0.534        (e)        P=0.124    |  P=0.148        (e)        P=0.548      P=0.349    |
|LOGISTIC REGRESSION    |  P=0.045 *    P=0.515        (e)        P=0.125    |  P=0.067        (e)        P=0.548      P=0.240    |
|COCHRAN-ARMITAGE       |  P=0.044 *                                         |  P=0.071                                           |
|FISHER EXACT           |               P=0.496        (e)        P=0.119    |                 (e)        P=0.500      P=0.252    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE  15
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, or Fibrous Histiocytoma                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/64 (0%)    1/63 (2%)    1/63 (2%)    3/63 (5%)  |  1/63 (2%)    0/63 (0%)    1/63 (2%)    2/64 (3%)  |
|ADJUSTED (b)           |   0.0%         4.3%         4.0%        10.5%      |   2.8%         0.0%         3.6%         5.5%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    0/18 (0%)    1/21 (5%)  |  0/22 (0%)    0/17 (0%)    1/28 (4%)    1/29 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          704          711          628       |   666          ---          729 (T)      480       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.073      P=0.518      P=0.545      P=0.161    |  P=0.296      P=0.589N     P=0.731N     P=0.513    |
|INCIDENTAL TUMOR       |  P=0.035 *    P=0.534      P=0.473      P=0.124    |  P=0.330      P=0.557N     P=0.727N     P=0.545    |
|LOGISTIC REGRESSION    |  P=0.055      P=0.515      P=0.515      P=0.125    |  P=0.239      P=0.517N     P=0.747N     P=0.496    |
|COCHRAN-ARMITAGE       |  P=0.054                                           |  P=0.249                                           |
|FISHER EXACT           |               P=0.496      P=0.496      P=0.119    |               P=0.500N     P=0.752N     P=0.506    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Keratoacanthoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/64 (8%)    1/63 (2%)    1/63 (2%)    0/63 (0%)  |  0/63 (0%)    0/63 (0%)    0/63 (0%)    0/64 (0%)  |
|ADJUSTED (b)           |  18.7%         4.3%         3.6%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  1/5 (20%)    0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  1/16 (6%)    0/16 (0%)    0/18 (0%)    0/21 (0%)  |  0/22 (0%)    0/17 (0%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   458 (I)      704          685          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.014N*    P=0.099N     P=0.088N     P=0.030N*  |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.024N*    P=0.079N     P=0.118N     P=0.049N*  |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.016N*    P=0.097N     P=0.101N     P=0.033N*  |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.017N*                                         |    (e)                                             |
|FISHER EXACT           |               P=0.107N     P=0.107N     P=0.030N*  |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE  16
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/64 (0%)    0/63 (0%)    2/63 (3%)    2/63 (3%)  |  0/63 (0%)    0/63 (0%)    0/63 (0%)    0/64 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%        11.1%         9.5%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    2/18 (11%)   2/21 (10%) |  0/22 (0%)    0/17 (0%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          733 (T)      733 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.129        (e)        P=0.263      P=0.299    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.129        (e)        P=0.263      P=0.299    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.129        (e)        P=0.263      P=0.299    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.084                                           |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.244      P=0.244    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma, Papilloma, Squamous Cell Carcinoma or Keratoacanthoma                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/64 (8%)    2/63 (3%)    3/63 (5%)    2/63 (3%)  |  1/63 (2%)    0/63 (0%)    0/63 (0%)    0/64 (0%)  |
|ADJUSTED (b)           |  18.7%        10.3%        14.3%         9.5%      |   2.1%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  1/5 (20%)    0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  1/16 (6%)    1/16 (6%)    2/18 (11%)   2/21 (10%) |  0/22 (0%)    0/17 (0%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   458 (I)      704          685          733 (T)   |   566          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.158N     P=0.206N     P=0.305N     P=0.172N   |  P=0.323N     P=0.513N     P=0.488N     P=0.536N   |
|INCIDENTAL TUMOR       |  P=0.220N     P=0.180N     P=0.369N     P=0.233N   |  P=0.486N     P=0.372N     P=0.602N     P=0.814N   |
|LOGISTIC REGRESSION    |  P=0.203N     P=0.200N     P=0.343N     P=0.207N   |  P=0.301N     P=0.494N     P=0.504N     P=0.487N   |
|COCHRAN-ARMITAGE       |  P=0.220N                                          |  P=0.307N                                          |
|FISHER EXACT           |               P=0.226N     P=0.368N     P=0.226N   |               P=0.500N     P=0.500N     P=0.496N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE  17
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma, Papilloma, or Keratoacanthoma                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/64 (8%)    1/63 (2%)    3/63 (5%)    2/63 (3%)  |  0/63 (0%)    0/63 (0%)    0/63 (0%)    0/64 (0%)  |
|ADJUSTED (b)           |  18.7%         4.3%        14.3%         9.5%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  1/5 (20%)    0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  1/16 (6%)    0/16 (0%)    2/18 (11%)   2/21 (10%) |  0/22 (0%)    0/17 (0%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   458 (I)      704          685          733 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.197N     P=0.099N     P=0.305N     P=0.172N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.273N     P=0.079N     P=0.369N     P=0.233N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.244N     P=0.097N     P=0.343N     P=0.207N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.260N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.107N     P=0.368N     P=0.226N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 50/59 (85%)  51/58 (88%)  50/58 (86%)  54/58 (93%) |                                                    |
|ADJUSTED (b)           | 100.0%        98.0%        98.0%        98.2%      |                                                    |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |                                                    |
|INTERIM SACRIFICE 2 (c)|  5/5 (100%)   5/5 (100%)   5/5 (100%)   4/5 (80%)  |                                                    |
|TERMINAL (d)           | 16/16 (100%) 15/16 (94%)  17/18 (94%)  20/21 (95%) |                                                    |
|FIRST INCIDENCE (DAYS) |   458 (I)      458 (I)      458 (I)      320       |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.379N     P=0.474N     P=0.367N     P=0.417N   |                                                    |
|INCIDENTAL TUMOR       |  P=0.118      P=0.573N     P=0.574N     P=0.172    |                                                    |
|LOGISTIC REGRESSION    |  P=0.109      P=0.581      P=0.610      P=0.146    |                                                    |
|COCHRAN-ARMITAGE       |  P=0.117                                           |                                                    |
|FISHER EXACT           |               P=0.409      P=0.515      P=0.126    |                                                    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE  18
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  8/58 (14%)   1/58 (2%)    2/56 (4%)    1/57 (2%)  |  1/57 (2%)    2/58 (3%)    4/58 (7%)    2/57 (4%)  |
|ADJUSTED (b)           |  37.6%         6.3%         6.8%         4.8%      |   2.2%         8.4%        10.6%         6.9%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  4/16 (25%)   1/16 (6%)    0/18 (0%)    1/21 (5%)  |  0/22 (0%)    1/17 (6%)    1/28 (4%)    2/29 (7%)  |
|FIRST INCIDENCE (DAYS) |   577          733 (T)      538          733 (T)   |   621          619          648          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.008N**   P=0.018N*    P=0.036N*    P=0.008N** |  P=0.476      P=0.419      P=0.224      P=0.547    |
|INCIDENTAL TUMOR       |  P=0.015N*    P=0.013N*    P=0.060N     P=0.014N*  |  P=0.268      P=0.617      P=0.174      P=0.402    |
|LOGISTIC REGRESSION    |  P=0.013N*    P=0.012N*    P=0.045N*    P=0.012N*  |  P=0.379      P=0.495      P=0.186      P=0.483    |
|COCHRAN-ARMITAGE       |  P=0.016N*                                         |  P=0.384                                           |
|FISHER EXACT           |               P=0.016N*    P=0.053N     P=0.017N*  |               P=0.507      P=0.187      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/58 (0%)    1/58 (2%)    0/56 (0%)    2/57 (4%)  |  1/57 (2%)    0/58 (0%)    2/58 (3%)    3/57 (5%)  |
|ADJUSTED (b)           |   0.0%         2.7%         0.0%         7.9%      |   4.5%         0.0%         7.1%         9.5%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    0/18 (0%)    1/21 (5%)  |  1/22 (5%)    0/17 (0%)    2/28 (7%)    2/29 (7%)  |
|FIRST INCIDENCE (DAYS) |   ---          643          ---          671       |   729 (T)      ---          729 (T)      661       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.158      P=0.529        (e)        P=0.282    |  P=0.176      P=0.551N     P=0.585      P=0.379    |
|INCIDENTAL TUMOR       |  P=0.138      P=0.529        (e)        P=0.226    |  P=0.153      P=0.551N     P=0.585      P=0.327    |
|LOGISTIC REGRESSION    |  P=0.142      P=0.501        (e)        P=0.248    |  P=0.127      P=0.551N     P=0.585      P=0.300    |
|COCHRAN-ARMITAGE       |  P=0.139                                           |  P=0.100                                           |
|FISHER EXACT           |               P=0.500        (e)        P=0.243    |               P=0.496N     P=0.507      P=0.309    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE  19
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  8/58 (14%)   2/58 (3%)    2/56 (4%)    3/57 (5%)  |  2/57 (4%)    2/58 (3%)    6/58 (10%)   5/57 (9%)  |
|ADJUSTED (b)           |  37.6%         8.8%         6.8%        12.5%      |   6.7%         8.4%        17.3%        16.2%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  4/16 (25%)   1/16 (6%)    0/18 (0%)    2/21 (10%) |  1/22 (5%)    1/17 (6%)    3/28 (11%)   4/29 (14%) |
|FIRST INCIDENCE (DAYS) |   577          643          538          671       |   621          619          648          661       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.062N     P=0.046N*    P=0.036N*    P=0.054N   |  P=0.206      P=0.604      P=0.200      P=0.292    |
|INCIDENTAL TUMOR       |  P=0.100N     P=0.037N*    P=0.060N     P=0.089N   |  P=0.087      P=0.630N     P=0.163      P=0.178    |
|LOGISTIC REGRESSION    |  P=0.091N     P=0.034N*    P=0.045N*    P=0.077N   |  P=0.110      P=0.666      P=0.153      P=0.200    |
|COCHRAN-ARMITAGE       |  P=0.104N                                          |  P=0.108                                           |
|FISHER EXACT           |               P=0.047N*    P=0.053N     P=0.107N   |               P=0.684N     P=0.141      P=0.219    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/58 (0%)    0/58 (0%)    1/56 (2%)    1/57 (2%)  |  0/57 (0%)    2/58 (3%)    0/58 (0%)    0/57 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         4.5%         4.8%      |   0.0%         7.7%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    0/18 (0%)    1/21 (5%)  |  0/22 (0%)    0/17 (0%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          725          733 (T)   |   ---          627          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.280        (e)        P=0.540      P=0.554    |  P=0.376N     P=0.179        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.219        (e)        P=0.459      P=0.554    |  P=0.590N     P=0.272        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.254        (e)        P=0.519      P=0.554    |  P=0.397N     P=0.230        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.230                                           |  P=0.395N                                          |
|FISHER EXACT           |                 (e)        P=0.491      P=0.496    |               P=0.252        (e)          (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE  20
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  5/63 (8%)    3/63 (5%)    4/63 (6%)    7/64 (11%) |
|ADJUSTED (b)           |                                                    |  13.9%        13.6%        11.2%        20.3%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|                                                    |  1/5 (20%)    0/5 (0%)     1/5 (20%)    0/5 (0%)   |
|TERMINAL (d)           |                                                    |  1/22 (5%)    1/17 (6%)    2/28 (7%)    4/29 (14%) |
|FIRST INCIDENCE (DAYS) |                                                    |   459 (I)      656          459 (I)      538       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.331      P=0.513N     P=0.430N     P=0.438    |
|INCIDENTAL TUMOR       |                                                    |  P=0.249      P=0.429N     P=0.472N     P=0.359    |
|LOGISTIC REGRESSION    |                                                    |  P=0.207      P=0.386N     P=0.497N     P=0.354    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.228                                           |
|FISHER EXACT           |                                                    |               P=0.359N     P=0.500N     P=0.393    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  5/63 (8%)    3/63 (5%)    4/63 (6%)    8/64 (13%) |
|ADJUSTED (b)           |                                                    |  13.9%        13.6%        11.2%        22.9%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|                                                    |  1/5 (20%)    0/5 (0%)     1/5 (20%)    0/5 (0%)   |
|TERMINAL (d)           |                                                    |  1/22 (5%)    1/17 (6%)    2/28 (7%)    4/29 (14%) |
|FIRST INCIDENCE (DAYS) |                                                    |   459 (I)      656          459 (I)      538       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.229      P=0.513N     P=0.430N     P=0.342    |
|INCIDENTAL TUMOR       |                                                    |  P=0.144      P=0.429N     P=0.472N     P=0.231    |
|LOGISTIC REGRESSION    |                                                    |  P=0.123      P=0.386N     P=0.497N     P=0.252    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.140                                           |
|FISHER EXACT           |                                                    |               P=0.359N     P=0.500N     P=0.290    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE  21
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|Zymbal's Gland                                                                                                                   |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/64 (2%)    0/63 (0%)    2/63 (3%)    0/63 (0%)  |  0/63 (0%)    0/63 (0%)    1/63 (2%)    0/64 (0%)  |
|ADJUSTED (b)           |   3.7%         0.0%         4.6%         0.0%      |   0.0%         0.0%         1.9%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    0/18 (0%)    0/21 (0%)  |  0/22 (0%)    0/17 (0%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   679          ---          279          ---       |   ---          ---          510          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.455N     P=0.472N     P=0.518      P=0.493N   |  P=0.679        (e)        P=0.504        (e)      |
|INCIDENTAL TUMOR       |  P=0.562N     P=0.466N     P=0.415      P=0.575N   |  P=0.676N       (e)        P=0.318        (e)      |
|LOGISTIC REGRESSION    |  P=0.474N     P=0.490N     P=0.484      P=0.495N   |  P=0.710        (e)        P=0.494        (e)      |
|COCHRAN-ARMITAGE       |  P=0.469N                                          |  P=0.693                                           |
|FISHER EXACT           |               P=0.504N     P=0.494      P=0.504N   |                 (e)        P=0.500        (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 31/64 (48%)  36/63 (57%)  39/63 (62%)  38/63 (60%) | 25/63 (40%)  26/63 (41%)  34/63 (54%)  23/64 (36%) |
|ADJUSTED (b)           |  81.4%        89.0%        90.3%        82.2%      |  62.0%        67.5%        67.1%        54.2%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     1/5 (20%)    0/5 (0%)   |  0/5 (0%)     1/5 (20%)    1/5 (20%)    0/5 (0%)   |
|TERMINAL (d)           | 10/16 (63%)  12/16 (75%)  14/18 (78%)  13/21 (62%) |  8/22 (36%)   7/17 (41%)  12/28 (43%)  10/29 (34%) |
|FIRST INCIDENCE (DAYS) |   496          539          458 (I)      539       |   503          459 (I)      403          475       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.444      P=0.383      P=0.283      P=0.424    |  P=0.191N     P=0.179      P=0.312      P=0.308N   |
|INCIDENTAL TUMOR       |  P=0.080      P=0.170      P=0.079      P=0.096    |  P=0.199      P=0.559      P=0.039 *    P=0.289    |
|LOGISTIC REGRESSION    |  P=0.048 *    P=0.290      P=0.060      P=0.060    |  P=0.258      P=0.547      P=0.050 *    P=0.351    |
|COCHRAN-ARMITAGE       |  P=0.116                                           |  P=0.401N                                          |
|FISHER EXACT           |               P=0.211      P=0.089      P=0.122    |               P=0.500      P=0.076      P=0.400N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE  22
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma: Benign, Malignant, NOS                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/64 (0%)    2/63 (3%)    0/63 (0%)    0/63 (0%)  |  0/63 (0%)    0/63 (0%)    0/63 (0%)    0/64 (0%)  |
|ADJUSTED (b)           |   0.0%         3.9%         0.0%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/16 (0%)    0/16 (0%)    0/18 (0%)    0/21 (0%)  |  0/22 (0%)    0/17 (0%)    0/28 (0%)    0/29 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          363          ---          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.391N     P=0.250        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.461N     P=0.255        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.405N     P=0.213        (e)          (e)      |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.397N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.244        (e)          (e)      |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 54/64 (84%)  55/63 (87%)  55/63 (87%)  55/63 (87%) | 36/63 (57%)  42/63 (67%)  36/63 (57%)  36/64 (56%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  82.4%        90.9%        83.0%        87.6%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  5/5 (100%)   5/5 (100%)   5/5 (100%)   4/5 (80%)  |  1/5 (20%)    0/5 (0%)     1/5 (20%)    0/5 (0%)   |
|TERMINAL (d)           | 16/16 (100%) 16/16 (100%) 18/18 (100%) 21/21 (100%)| 15/22 (68%)  13/17 (76%)  21/28 (75%)  24/29 (83%) |
|FIRST INCIDENCE (DAYS) |   458 (I)      458 (I)      432          320       |   459 (I)      392          459 (I)      480       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.239N     P=0.458N     P=0.424N     P=0.275N   |  P=0.065N     P=0.028 *    P=0.230N     P=0.283N   |
|INCIDENTAL TUMOR       |  P=0.454      P=0.587      P=0.554      P=0.504    |  P=0.524N     P=0.111      P=0.389N     P=0.326    |
|LOGISTIC REGRESSION    |  P=0.323      P=0.522      P=0.466      P=0.422    |  P=0.400      P=0.066      P=0.447N     P=0.333    |
|COCHRAN-ARMITAGE       |  P=0.390                                           |  P=0.333N                                          |
|FISHER EXACT           |               P=0.414      P=0.414      P=0.414    |               P=0.180      P=0.571N     P=0.531N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE  23
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |   0.0MG/M3     0.12MGM3     0.25MGM3     0.5MG/M3  |
|                       |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |   LUNG TOX     LUNG TOX     LUNG TOX     LUNG TOX  |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 37/64 (58%)  43/63 (68%)  42/63 (67%)  41/63 (65%) | 35/63 (56%)  34/63 (54%)  38/63 (60%)  29/64 (45%) |
|ADJUSTED (b)           |  88.8%        93.1%        91.0%        86.9%      |  73.5%        80.8%        72.5%        64.0%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     1/5 (20%)    0/5 (0%)   |  0/5 (0%)     1/5 (20%)    1/5 (20%)    0/5 (0%)   |
|TERMINAL (d)           | 12/16 (75%)  13/16 (81%)  14/18 (78%)  15/21 (71%) | 10/22 (45%)  10/17 (59%)  14/28 (50%)  13/29 (45%) |
|FIRST INCIDENCE (DAYS) |   262          539          279          320       |   503          459 (I)      403          272       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.383N     P=0.361      P=0.447      P=0.494N   |  P=0.065N     P=0.210      P=0.432N     P=0.152N   |
|INCIDENTAL TUMOR       |  P=0.230      P=0.096      P=0.167      P=0.216    |  P=0.446      P=0.372N     P=0.194      P=0.500    |
|LOGISTIC REGRESSION    |  P=0.291      P=0.204      P=0.212      P=0.275    |  P=0.490N     P=0.387N     P=0.229      P=0.271N   |
|COCHRAN-ARMITAGE       |  P=0.305                                           |  P=0.150N                                          |
|FISHER EXACT           |               P=0.150      P=0.199      P=0.255    |               P=0.500N     P=0.359      P=0.164N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 58/64 (91%)  57/63 (90%)  57/63 (90%)  55/63 (87%) | 50/63 (79%)  53/63 (84%)  52/63 (83%)  48/64 (75%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  96.1%        98.1%        96.3%        98.0%      |
|INTERIM SACRIFICE 1 (c)|  0/5 (0%)     0/5 (0%)     1/5 (20%)    0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  5/5 (100%)   5/5 (100%)   5/5 (100%)   4/5 (80%)  |  1/5 (20%)    1/5 (20%)    2/5 (40%)    0/5 (0%)   |
|TERMINAL (d)           | 16/16 (100%) 16/16 (100%) 18/18 (100%) 21/21 (100%)| 20/22 (91%)  16/17 (94%)  26/28 (93%)  28/29 (97%) |
|FIRST INCIDENCE (DAYS) |   262          363          199 (I)      320       |   459 (I)      392          403          272       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.125N     P=0.363N     P=0.337N     P=0.144N   |  P=0.042N*    P=0.045 *    P=0.248N     P=0.181N   |
|INCIDENTAL TUMOR       |  P=0.143N     P=0.807      P=0.605N     P=0.233N   |  P=0.520      P=0.261      P=0.449      P=0.386    |
|LOGISTIC REGRESSION    |  P=0.126N     P=0.324N     P=0.515N     P=0.167N   |  P=0.442      P=0.196      P=0.494      P=0.317    |
|COCHRAN-ARMITAGE       |  P=0.303N                                          |  P=0.224N                                          |
|FISHER EXACT           |               P=0.607N     P=0.607N     P=0.377N   |               P=0.323      P=0.410      P=0.354N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05122 TEST: 05                                                 PAGE  24
                       STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL SULFATE HEXAHYDRATE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
                                                                           
 (a)  Number of tumor-bearing animals / number of animals examined at site.
 (b)  Kaplan-Meier estimated lifetime tumor incidence after adjustment for 
      intercurrent mortality.
 (c)  Observed incidence at interim kill.
          Male interim sacrifices(days):   199  458
          Female interim sacrifices(days): 200  459
 (d)  Observed incidence at terminal kill.
 (f)  Beneath the control incidence are the P-values associated with the trend 
      test.  Beneath the dosed group incidence are the P-values corresponding to 
      pairwise comparisons between the controls and that dosed group.  The life
      table analysis regards tumors in animals dying  prior to terminal kill as
      being (directly or indirectly) the cause of death.  The incidental tumor 
      test regards these lesions as non-fatal.  Logistic regression is an alternative
      method for analyzing the incidence of non-fatal tumors.  The Cochran-Armitage
      and Fisher's exact tests compare directly the overall incidence rates.  
      For all tests, a negative trend is indicated by "N".
 (e)  Value of Statistic cannot be computed. 
 (I)  Interim sacrifice
 (T)  Terminal sacrifice
  #   Tumor rates based on number of animals necropsied.
  *   To the right of any statistical result, indicates significance at (P<=0.05).
  **  To the right of any statistical result, indicates significance at (P<=0.01).
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.