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TDMS Study 05123-06 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: LITRI                                                    NICKEL OXIDE                                     DATE: 05/20/95       
EXPERIMENT: 05123 TEST: 06                                                                                     TIME: 05:42:10       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: Y0-ES-30108                               ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C00862       
PATHOLOGIST: P. HALEY                                                                                          CAS: 1313-99-1       
------------------------------------------------------------------------------------------------------------------------------------
               REASONS FOR REMOVAL:    ALL                                                                                          
               REMOVAL DATE RANGE:     ALL                                                                                          
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: LITRI                                                    NICKEL OXIDE                                     DATE: 05/20/95       
EXPERIMENT: 05123 TEST: 06                                                                                     TIME: 05:42:10       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: Y0-ES-30108                               ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C00862       
PATHOLOGIST: P. HALEY                                                                                          CAS: 1313-99-1       
                                                    MICE(B6C3F1)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
                                                    ----------------
                                                    Adrenal Cortex
                                                    Adrenal Medulla
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Epididymis
                                                    Gallbladder
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Larynx
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: LITRI                                                    NICKEL OXIDE                                     DATE: 05/20/95       
EXPERIMENT: 05123 TEST: 06                                                                                     TIME: 05:42:10       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: Y0-ES-30108                               ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C00862       
PATHOLOGIST: P. HALEY                                                                                          CAS: 1313-99-1       
                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                          IN THE ANALYSIS OF THE STUDY OF NICKEL OXIDE
              ====================================================================================================
                                                           MALE MICE
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------
              Adrenal Cortex                Adenoma
              Liver                         Hepatocellular Carcinoma
                                            Hepatocellular Carcinoma or Hepatocellular Adenoma
                                            Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma
              All Organs                    Malignant Tumors
              ====================================================================================================
                                                           FEMALE MICE
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------
              Harderian Gland               Adenoma
              Lung                          Alveolar/Bronchiolar Adenoma
                                            Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
              All Organs                    Malignant and Benign Tumors
              ====================================================================================================
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE   1
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/62 (6%)    0/72 (0%)    1/70 (1%)    1/74 (1%)  |  0/69 (0%)    0/71 (0%)    0/68 (0%)    1/67 (1%)  |
|ADJUSTED (b)           |  21.1%         0.0%         3.6%         3.7%      |   0.0%         0.0%         0.0%         2.6%      |
|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)           |  4/19 (21%)   0/23 (0%)    1/28 (4%)    0/23 (0%)  |  0/41 (0%)    0/40 (0%)    0/42 (0%)    1/38 (3%)  |
|FIRST INCIDENCE (DAYS) |   737 (T)      ---          737 (T)      716       |   ---          ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.122N     P=0.039N*    P=0.079N     P=0.120N   |  P=0.188        (e)          (e)        P=0.485    |
|INCIDENTAL TUMOR       |  P=0.115N     P=0.039N*    P=0.079N     P=0.109N   |  P=0.188        (e)          (e)        P=0.485    |
|LOGISTIC REGRESSION    |  P=0.113N     P=0.039N*    P=0.079N     P=0.101N   |  P=0.188        (e)          (e)        P=0.485    |
|COCHRAN-ARMITAGE       |  P=0.139N                                          |  P=0.192                                           |
|FISHER EXACT           |               P=0.043N*    P=0.147N     P=0.133N   |                 (e)          (e)        P=0.493    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Malignant                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/62 (0%)    0/72 (0%)    0/70 (0%)    0/73 (0%)  |  2/67 (3%)    0/70 (0%)    0/68 (0%)    0/67 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   4.2%         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)           |  0/19 (0%)    0/23 (0%)    0/28 (0%)    0/23 (0%)  |  0/41 (0%)    0/39 (0%)    0/42 (0%)    0/38 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   599          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.120N     P=0.229N     P=0.247N     P=0.238N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.115N     P=0.146N     P=0.250N     P=0.189N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.118N     P=0.227N     P=0.235N     P=0.236N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.118N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.237N     P=0.244N     P=0.248N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE   2
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/62 (0%)    0/72 (0%)    0/70 (0%)    0/73 (0%)  |  3/67 (4%)    0/70 (0%)    1/68 (1%)    0/67 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   6.5%         0.0%         2.4%         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)           |  0/19 (0%)    0/23 (0%)    0/28 (0%)    0/23 (0%)  |  1/41 (2%)    0/39 (0%)    1/42 (2%)    0/38 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   599          ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.094N     P=0.121N     P=0.310N     P=0.128N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.091N     P=0.077N     P=0.312N     P=0.101N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.089N     P=0.110N     P=0.302N     P=0.118N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.090N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.114N     P=0.304N     P=0.122N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Harderian Gland                                                                                                                  |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/67 (0%)    1/77 (1%)    2/76 (3%)    2/79 (3%)  |  0/74 (0%)    1/76 (1%)    2/73 (3%)    3/74 (4%)  |
|ADJUSTED (b)           |   0.0%         4.3%         5.5%         7.8%      |   0.0%         1.8%         4.4%         7.9%      |
|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)           |  0/19 (0%)    1/23 (4%)    1/29 (3%)    1/23 (4%)  |  0/41 (0%)    0/40 (0%)    1/42 (2%)    3/38 (8%)  |
|FIRST INCIDENCE (DAYS) |   ---          737 (T)      649          714       |   ---          609          640          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.197      P=0.538      P=0.341      P=0.299    |  P=0.058      P=0.519      P=0.247      P=0.108    |
|INCIDENTAL TUMOR       |  P=0.216      P=0.538      P=0.356      P=0.321    |  P=0.048 *    P=0.523      P=0.211      P=0.108    |
|LOGISTIC REGRESSION    |  P=0.203      P=0.538      P=0.303      P=0.300    |  P=0.063      P=0.507      P=0.239      P=0.108    |
|COCHRAN-ARMITAGE       |  P=0.189                                           |  P=0.061                                           |
|FISHER EXACT           |               P=0.535      P=0.281      P=0.291    |               P=0.507      P=0.245      P=0.122    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE   3
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/63 (2%)    1/72 (1%)    0/73 (0%)    2/74 (3%)  |  0/69 (0%)    1/71 (1%)    1/68 (1%)    1/68 (1%)  |
|ADJUSTED (b)           |   2.2%         3.6%         0.0%         6.9%      |   0.0%         1.9%         2.4%         2.0%      |
|INTERIM SACRIFICE 1 (c)|  0/1 (0%)     0/0          0/2 (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)           |  0/19 (0%)    0/23 (0%)    0/29 (0%)    0/23 (0%)  |  0/41 (0%)    0/40 (0%)    1/42 (2%)    0/38 (0%)  |
|FIRST INCIDENCE (DAYS) |   559          717          ---          704       |   ---          640          729 (T)      640       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.423      P=0.716N     P=0.475N     P=0.586    |  P=0.388      P=0.524      P=0.505      P=0.516    |
|INCIDENTAL TUMOR       |  P=0.440      P=0.758N     P=0.731N     P=0.589    |  P=0.344      P=0.523      P=0.505      P=0.473    |
|LOGISTIC REGRESSION    |  P=0.417      P=0.729N     P=0.484N     P=0.571    |  P=0.386      P=0.508      P=0.505      P=0.500    |
|COCHRAN-ARMITAGE       |  P=0.404                                           |  P=0.379                                           |
|FISHER EXACT           |               P=0.717N     P=0.463N     P=0.561    |               P=0.507      P=0.496      P=0.496    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 10/63 (16%)   6/72 (8%)   17/73 (23%)   9/74 (12%) |  6/69 (9%)    8/71 (11%)   9/68 (13%)   5/68 (7%)  |
|ADJUSTED (b)           |  37.2%        19.3%        36.4%        26.3%      |  14.6%        18.3%        19.7%        12.5%      |
|INTERIM SACRIFICE 1 (c)|  1/1 (100%)   0/0          2/2 (100%)   0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  1/5 (20%)    1/5 (20%)    2/5 (40%)    0/5 (0%)   |  0/5 (0%)     1/5 (20%)    0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  5/19 (26%)   3/23 (13%)   7/29 (24%)   4/23 (17%) |  6/41 (15%)   6/40 (15%)   6/42 (14%)   3/38 (8%)  |
|FIRST INCIDENCE (DAYS) |   199 (I)      458 (I)      199 (I)      431       |   729 (T)      459 (I)      640          720       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.529      P=0.185N     P=0.403      P=0.423N   |  P=0.438N     P=0.371      P=0.307      P=0.553N   |
|INCIDENTAL TUMOR       |  P=0.534      P=0.204N     P=0.360      P=0.389N   |  P=0.379N     P=0.412      P=0.308      P=0.458N   |
|LOGISTIC REGRESSION    |  P=0.519N     P=0.128N     P=0.186      P=0.332N   |  P=0.397N     P=0.447      P=0.286      P=0.542N   |
|COCHRAN-ARMITAGE       |  P=0.529N                                          |  P=0.413N                                          |
|FISHER EXACT           |               P=0.139N     P=0.194      P=0.351N   |               P=0.412      P=0.282      P=0.510N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE   4
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  7/63 (11%)  17/72 (24%)  12/73 (16%)  15/74 (20%) |  8/69 (12%)  10/71 (14%)   8/68 (12%)   4/68 (6%)  |
|ADJUSTED (b)           |  20.4%        38.6%        26.0%        39.5%      |  18.1%        21.0%        16.2%         9.2%      |
|INTERIM SACRIFICE 1 (c)|  0/1 (0%)     0/0          0/2 (0%)     0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  1/5 (20%)    1/5 (20%)    1/5 (20%)    0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  1/19 (5%)    2/23 (9%)    3/29 (10%)   5/23 (22%) |  6/41 (15%)   5/40 (13%)   4/42 (10%)   2/38 (5%)  |
|FIRST INCIDENCE (DAYS) |   392          341          458 (I)      459       |   586          469          451          644       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.288      P=0.081      P=0.384      P=0.144    |  P=0.126N     P=0.409      P=0.591N     P=0.208N   |
|INCIDENTAL TUMOR       |  P=0.275      P=0.077      P=0.315      P=0.120    |  P=0.067N     P=0.583      P=0.584N     P=0.163N   |
|LOGISTIC REGRESSION    |  P=0.227      P=0.048 *    P=0.263      P=0.119    |  P=0.102N     P=0.475      P=0.602N     P=0.167N   |
|COCHRAN-ARMITAGE       |  P=0.236                                           |  P=0.116N                                          |
|FISHER EXACT           |               P=0.046 *    P=0.261      P=0.110    |               P=0.426      P=0.592      P=0.190N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 15/63 (24%)  22/72 (31%)  28/73 (38%)  20/74 (27%) | 14/69 (20%)  17/71 (24%)  17/68 (25%)   9/68 (13%) |
|ADJUSTED (b)           |  44.4%        48.4%        53.9%        49.3%      |  32.2%        34.9%        33.9%        20.9%      |
|INTERIM SACRIFICE 1 (c)|  1/1 (100%)   0/0          2/2 (100%)   0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  2/5 (40%)    2/5 (40%)    3/5 (60%)    0/5 (0%)   |  0/5 (0%)     1/5 (20%)    0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  5/19 (26%)   4/23 (17%)  10/29 (34%)   7/23 (30%) | 12/41 (29%)  10/40 (25%)  10/42 (24%)   5/38 (13%) |
|FIRST INCIDENCE (DAYS) |   199 (I)      341          199 (I)      431       |   586          459 (I)      451          644       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.443      P=0.255      P=0.197      P=0.379    |  P=0.156N     P=0.339      P=0.365      P=0.227N   |
|INCIDENTAL TUMOR       |  P=0.424      P=0.249      P=0.110      P=0.347    |  P=0.077N     P=0.505      P=0.369      P=0.142N   |
|LOGISTIC REGRESSION    |  P=0.440      P=0.253      P=0.047 *    P=0.427    |  P=0.110N     P=0.443      P=0.345      P=0.163N   |
|COCHRAN-ARMITAGE       |  P=0.428                                           |  P=0.134N                                          |
|FISHER EXACT           |               P=0.248      P=0.051      P=0.409    |               P=0.376      P=0.325      P=0.191N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE   5
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 15/63 (24%)  22/72 (31%)  28/73 (38%)  20/74 (27%) | 14/69 (20%)  17/71 (24%)  17/68 (25%)   9/68 (13%) |
|ADJUSTED (b)           |  44.4%        48.4%        53.9%        49.3%      |  32.2%        34.9%        33.9%        20.9%      |
|INTERIM SACRIFICE 1 (c)|  1/1 (100%)   0/0          2/2 (100%)   0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  2/5 (40%)    2/5 (40%)    3/5 (60%)    0/5 (0%)   |  0/5 (0%)     1/5 (20%)    0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  5/19 (26%)   4/23 (17%)  10/29 (34%)   7/23 (30%) | 12/41 (29%)  10/40 (25%)  10/42 (24%)   5/38 (13%) |
|FIRST INCIDENCE (DAYS) |   199 (I)      341          199 (I)      431       |   586          459 (I)      451          644       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.443      P=0.255      P=0.197      P=0.379    |  P=0.156N     P=0.339      P=0.365      P=0.227N   |
|INCIDENTAL TUMOR       |  P=0.424      P=0.249      P=0.110      P=0.347    |  P=0.077N     P=0.505      P=0.369      P=0.142N   |
|LOGISTIC REGRESSION    |  P=0.440      P=0.253      P=0.047 *    P=0.427    |  P=0.110N     P=0.443      P=0.345      P=0.163N   |
|COCHRAN-ARMITAGE       |  P=0.428                                           |  P=0.134N                                          |
|FISHER EXACT           |               P=0.248      P=0.051      P=0.409    |               P=0.376      P=0.325      P=0.191N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  9/67 (13%)   5/77 (6%)    6/76 (8%)   11/79 (14%) |  2/74 (3%)    4/76 (5%)   11/73 (15%)   3/74 (4%)  |
|ADJUSTED (b)           |  32.6%        16.2%        18.3%        33.0%      |   4.7%         9.3%        22.7%         7.1%      |
|INTERIM SACRIFICE 1 (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%)   |
|INTERIM SACRIFICE 2 (c)|  1/5 (20%)    0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     1/5 (20%)    0/5 (0%)   |
|TERMINAL (d)           |  4/19 (21%)   2/23 (9%)    4/29 (14%)   5/23 (22%) |  1/41 (2%)    3/40 (8%)    6/42 (14%)   2/38 (5%)  |
|FIRST INCIDENCE (DAYS) |   199 (I)      512          676          489       |   728          652          459 (I)      619       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.367      P=0.126N     P=0.104N     P=0.586N   |  P=0.348      P=0.334      P=0.013 *    P=0.474    |
|INCIDENTAL TUMOR       |  P=0.374      P=0.110N     P=0.113N     P=0.594    |  P=0.398      P=0.449      P=0.011 *    P=0.528    |
|LOGISTIC REGRESSION    |  P=0.354      P=0.122N     P=0.147N     P=0.596N   |  P=0.381      P=0.366      P=0.010 **   P=0.512    |
|COCHRAN-ARMITAGE       |  P=0.322                                           |  P=0.368                                           |
|FISHER EXACT           |               P=0.131N     P=0.210N     P=0.563    |               P=0.353      P=0.008 **   P=0.500    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE   6
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  4/67 (6%)   10/77 (13%)   9/76 (12%)   6/79 (8%)  |  4/74 (5%)   11/76 (14%)   4/73 (5%)    5/74 (7%)  |
|ADJUSTED (b)           |  16.9%        32.4%        27.3%        19.6%      |   9.4%        22.8%         9.0%        10.8%      |
|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)           |  2/19 (11%)   5/23 (22%)   7/29 (24%)   3/23 (13%) |  3/41 (7%)    5/40 (13%)   3/42 (7%)    2/38 (5%)  |
|FIRST INCIDENCE (DAYS) |   559          616          483          571       |   694          583          630          469       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.449N     P=0.160      P=0.321      P=0.520    |  P=0.407N     P=0.057      P=0.633N     P=0.483    |
|INCIDENTAL TUMOR       |  P=0.469N     P=0.119      P=0.292      P=0.496    |  P=0.286N     P=0.134      P=0.639N     P=0.623N   |
|LOGISTIC REGRESSION    |  P=0.443N     P=0.141      P=0.268      P=0.521    |  P=0.367N     P=0.068      P=0.643      P=0.525    |
|COCHRAN-ARMITAGE       |  P=0.502N                                          |  P=0.384N                                          |
|FISHER EXACT           |               P=0.128      P=0.177      P=0.480    |               P=0.056      P=0.633      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 11/67 (16%)  14/77 (18%)  15/76 (20%)  14/79 (18%) |  6/74 (8%)   15/76 (20%)  13/73 (18%)   8/74 (11%) |
|ADJUSTED (b)           |  38.5%        41.4%        43.6%        39.7%      |  13.8%        30.8%        27.0%        17.4%      |
|INTERIM SACRIFICE 1 (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%)   |
|INTERIM SACRIFICE 2 (c)|  1/5 (20%)    0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     1/5 (20%)    0/5 (0%)   |
|TERMINAL (d)           |  5/19 (26%)   6/23 (26%)  11/29 (38%)   6/23 (26%) |  4/41 (10%)   8/40 (20%)   8/42 (19%)   4/38 (11%) |
|FIRST INCIDENCE (DAYS) |   199 (I)      512          483          489       |   694          583          459 (I)      469       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.534N     P=0.529      P=0.531N     P=0.555    |  P=0.530      P=0.034 *    P=0.079      P=0.363    |
|INCIDENTAL TUMOR       |  P=0.533      P=0.490      P=0.591N     P=0.512    |  P=0.412N     P=0.094      P=0.078      P=0.532    |
|LOGISTIC REGRESSION    |  P=0.539      P=0.503      P=0.526      P=0.546    |  P=0.473N     P=0.042 *    P=0.067      P=0.418    |
|COCHRAN-ARMITAGE       |  P=0.477                                           |  P=0.526N                                          |
|FISHER EXACT           |               P=0.478      P=0.385      P=0.506    |               P=0.034 *    P=0.065      P=0.390    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE   7
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/67 (0%)    0/77 (0%)    0/76 (0%)    0/79 (0%)  |  2/74 (3%)    3/76 (4%)    0/73 (0%)    3/74 (4%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   4.6%         7.5%         0.0%         7.4%      |
|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)           |  0/19 (0%)    0/23 (0%)    0/29 (0%)    0/23 (0%)  |  1/41 (2%)    3/40 (8%)    0/42 (0%)    1/38 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   694          729 (T)      ---          699       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.478      P=0.489      P=0.245N     P=0.472    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.549      P=0.560      P=0.217N     P=0.673    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.494      P=0.519      P=0.238N     P=0.505    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.499                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.513      P=0.252N     P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/67 (0%)    0/77 (0%)    0/76 (0%)    0/79 (0%)  |  2/74 (3%)    4/76 (5%)    0/73 (0%)    3/74 (4%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   4.6%         9.4%         0.0%         7.4%      |
|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)           |  0/19 (0%)    0/23 (0%)    0/29 (0%)    0/23 (0%)  |  1/41 (2%)    3/40 (8%)    0/42 (0%)    1/38 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   694          683          ---          699       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.547      P=0.334      P=0.245N     P=0.472    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.546N     P=0.449      P=0.217N     P=0.673    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.569      P=0.367      P=0.238N     P=0.505    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.569                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.353      P=0.252N     P=0.500    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE   8
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/67 (0%)    0/77 (0%)    0/76 (0%)    0/79 (0%)  |  2/74 (3%)    4/76 (5%)    0/73 (0%)    3/74 (4%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   4.6%         9.4%         0.0%         7.4%      |
|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)           |  0/19 (0%)    0/23 (0%)    0/29 (0%)    0/23 (0%)  |  1/41 (2%)    3/40 (8%)    0/42 (0%)    1/38 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   694          683          ---          699       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.547      P=0.334      P=0.245N     P=0.472    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.546N     P=0.449      P=0.217N     P=0.673    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.569      P=0.367      P=0.238N     P=0.505    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.569                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.353      P=0.252N     P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Cystadenoma                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  1/66 (2%)    0/71 (0%)    3/65 (5%)    0/68 (0%)  |
|ADJUSTED (b)           |                                                    |   2.6%         0.0%         7.1%         0.0%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |                                                    |  1/38 (3%)    0/40 (0%)    3/42 (7%)    0/38 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   729 (T)      ---          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.507N     P=0.490N     P=0.342      P=0.500N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.507N     P=0.490N     P=0.342      P=0.500N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.507N     P=0.490N     P=0.342      P=0.500N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.505N                                          |
|FISHER EXACT           |                                                    |               P=0.482N     P=0.304      P=0.493N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE   9
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Teratoma Benign                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  2/66 (3%)    1/71 (1%)    0/65 (0%)    0/68 (0%)  |
|ADJUSTED (b)           |                                                    |   2.9%         1.3%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |                                                    |  0/38 (0%)    0/40 (0%)    0/42 (0%)    0/38 (0%)  |
|FIRST INCIDENCE (DAYS) |                                                    |    92          162          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.099N     P=0.469N     P=0.241N     P=0.229N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.190N     P=0.719      P=0.290N     P=0.500N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.209N     P=0.651      P=0.304N     P=0.572N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.101N                                          |
|FISHER EXACT           |                                                    |               P=0.472N     P=0.252N     P=0.241N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/61 (0%)    0/67 (0%)    0/68 (0%)    0/71 (0%)  |  6/68 (9%)    9/71 (13%)   8/66 (12%)   6/67 (9%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |  14.1%        20.5%        18.8%        14.6%      |
|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)           |  0/19 (0%)    0/23 (0%)    0/27 (0%)    0/22 (0%)  |  5/41 (12%)   7/40 (18%)   7/41 (17%)   4/38 (11%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   694          597          640          673       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.504N     P=0.287      P=0.387      P=0.574    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.477N     P=0.362      P=0.390      P=0.560N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.473N     P=0.350      P=0.370      P=0.621N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.485N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.324      P=0.367      P=0.608    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE  10
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/61 (0%)    0/67 (0%)    0/68 (0%)    0/71 (0%)  |  7/68 (10%)   9/71 (13%)   8/66 (12%)   7/67 (10%) |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |  16.5%        20.5%        18.8%        16.5%      |
|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)           |  0/19 (0%)    0/23 (0%)    0/27 (0%)    0/22 (0%)  |  6/41 (15%)   7/40 (18%)   7/41 (17%)   4/38 (11%) |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   694          597          640          673       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.534N     P=0.388      P=0.498      P=0.564    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.499N     P=0.469      P=0.502      P=0.528N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.501N     P=0.461      P=0.482      P=0.608N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.515N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.432      P=0.475      P=0.599    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/67 (0%)    0/77 (0%)    0/76 (0%)    0/79 (0%)  |  1/74 (1%)    2/76 (3%)    0/73 (0%)    0/74 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   2.4%         4.8%         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)           |  0/19 (0%)    0/23 (0%)    0/29 (0%)    0/23 (0%)  |  1/41 (2%)    1/40 (3%)    0/42 (0%)    0/38 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   729 (T)      720          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.194N     P=0.492      P=0.495N     P=0.515N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.169N     P=0.582      P=0.495N     P=0.515N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.190N     P=0.505      P=0.495N     P=0.515N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.186N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.510      P=0.503N     P=0.500N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE  11
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Sarcoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/67 (0%)    0/77 (0%)    0/76 (0%)    0/79 (0%)  |  0/74 (0%)    2/76 (3%)    1/73 (1%)    1/74 (1%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   0.0%         3.5%         2.4%         2.6%      |
|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)|  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)           |  0/19 (0%)    0/23 (0%)    0/29 (0%)    0/23 (0%)  |  0/41 (0%)    0/40 (0%)    1/42 (2%)    1/38 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   ---          593          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.498      P=0.267      P=0.505      P=0.485    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.463      P=0.259      P=0.505      P=0.485    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.509      P=0.245      P=0.505      P=0.485    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.502                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.255      P=0.497      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/61 (2%)    1/72 (1%)    2/71 (3%)    1/74 (1%)  |  2/69 (3%)    2/72 (3%)    5/68 (7%)    2/68 (3%)  |
|ADJUSTED (b)           |   5.3%         2.2%         6.9%         1.4%      |   4.7%         4.8%        10.7%         4.4%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/1 (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)           |  1/19 (5%)    0/23 (0%)    2/29 (7%)    0/23 (0%)  |  1/41 (2%)    1/40 (3%)    3/42 (7%)    0/38 (0%)  |
|FIRST INCIDENCE (DAYS) |   737 (T)      604          737 (T)      271       |   728          720          538          658       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.600N     P=0.708N     P=0.647      P=0.719N   |  P=0.496      P=0.679      P=0.230      P=0.678    |
|INCIDENTAL TUMOR       |  P=0.601      P=0.758      P=0.647      P=0.722N   |  P=0.503N     P=0.558N     P=0.287      P=0.508N   |
|LOGISTIC REGRESSION    |  P=0.600N     P=0.722N     P=0.647      P=0.725N   |  P=0.519      P=0.693N     P=0.220      P=0.685N   |
|COCHRAN-ARMITAGE       |  P=0.601N                                          |  P=0.502                                           |
|FISHER EXACT           |               P=0.709N     P=0.557      P=0.701N   |               P=0.674N     P=0.214      P=0.685    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE  12
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Squamous Cell Carcinoma or Papilloma Squamous                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/67 (1%)    1/77 (1%)    0/76 (0%)    1/79 (1%)  |  2/74 (3%)    0/76 (0%)    0/73 (0%)    1/74 (1%)  |
|ADJUSTED (b)           |   5.3%         4.3%         0.0%         4.3%      |   4.9%         0.0%         0.0%         2.3%      |
|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)           |  1/19 (5%)    1/23 (4%)    0/29 (0%)    1/23 (4%)  |  2/41 (5%)    0/40 (0%)    0/42 (0%)    0/38 (0%)  |
|FIRST INCIDENCE (DAYS) |   737 (T)      737 (T)      ---          737 (T)   |   729 (T)      ---          ---          696       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.576N     P=0.720N     P=0.416N     P=0.720N   |  P=0.477N     P=0.244N     P=0.233N     P=0.518N   |
|INCIDENTAL TUMOR       |  P=0.576N     P=0.720N     P=0.416N     P=0.720N   |  P=0.443N     P=0.244N     P=0.233N     P=0.440N   |
|LOGISTIC REGRESSION    |  P=0.576N     P=0.720N     P=0.416N     P=0.720N   |  P=0.470N     P=0.244N     P=0.233N     P=0.498N   |
|COCHRAN-ARMITAGE       |  P=0.581N                                          |  P=0.469N                                          |
|FISHER EXACT           |               P=0.716N     P=0.469N     P=0.709N   |               P=0.242N     P=0.252N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/62 (0%)    0/71 (0%)    2/71 (3%)    0/74 (0%)  |                                                    |
|ADJUSTED (b)           |   0.0%         0.0%         5.5%         0.0%      |                                                    |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |                                                    |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |                                                    |
|TERMINAL (d)           |  0/19 (0%)    0/23 (0%)    1/29 (3%)    0/23 (0%)  |                                                    |
|FIRST INCIDENCE (DAYS) |   ---          ---          649          ---       |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.639        (e)        P=0.341        (e)      |                                                    |
|INCIDENTAL TUMOR       |  P=0.657        (e)        P=0.356        (e)      |                                                    |
|LOGISTIC REGRESSION    |  P=0.632        (e)        P=0.302        (e)      |                                                    |
|COCHRAN-ARMITAGE       |  P=0.621                                           |                                                    |
|FISHER EXACT           |                 (e)        P=0.283        (e)      |                                                    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE  13
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    2/72 (3%)    2/71 (3%)    2/74 (3%)  |  2/67 (3%)    1/71 (1%)    1/68 (1%)    1/69 (1%)  |
|ADJUSTED (b)           |   9.8%         8.7%         6.0%         8.7%      |   4.9%         2.3%         2.4%         2.1%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|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)           |  1/19 (5%)    2/23 (9%)    1/29 (3%)    2/23 (9%)  |  2/41 (5%)    0/40 (0%)    1/42 (2%)    0/38 (0%)  |
|FIRST INCIDENCE (DAYS) |   458 (I)      737 (T)      679          737 (T)   |   729 (T)      711          729 (T)      658       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.358N     P=0.434N     P=0.359N     P=0.429N   |  P=0.425N     P=0.506N     P=0.492N     P=0.513N   |
|INCIDENTAL TUMOR       |  P=0.374N     P=0.468N     P=0.462N     P=0.468N   |  P=0.373N     P=0.418N     P=0.492N     P=0.440N   |
|LOGISTIC REGRESSION    |  P=0.345N     P=0.419N     P=0.403N     P=0.401N   |  P=0.412N     P=0.487N     P=0.492N     P=0.489N   |
|COCHRAN-ARMITAGE       |  P=0.361N                                          |  P=0.407N                                          |
|FISHER EXACT           |               P=0.414N     P=0.420N     P=0.401N   |               P=0.478N     P=0.494N     P=0.489N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/60 (5%)    2/72 (3%)    2/71 (3%)    2/74 (3%)  |  3/67 (4%)    1/71 (1%)    1/68 (1%)    1/69 (1%)  |
|ADJUSTED (b)           |   9.8%         8.7%         6.0%         8.7%      |   7.3%         2.3%         2.4%         2.1%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|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)           |  1/19 (5%)    2/23 (9%)    1/29 (3%)    2/23 (9%)  |  3/41 (7%)    0/40 (0%)    1/42 (2%)    0/38 (0%)  |
|FIRST INCIDENCE (DAYS) |   458 (I)      737 (T)      679          737 (T)   |   729 (T)      711          729 (T)      658       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.358N     P=0.434N     P=0.359N     P=0.429N   |  P=0.258N     P=0.313N     P=0.297N     P=0.323N   |
|INCIDENTAL TUMOR       |  P=0.374N     P=0.468N     P=0.462N     P=0.468N   |  P=0.219N     P=0.246N     P=0.297N     P=0.266N   |
|LOGISTIC REGRESSION    |  P=0.345N     P=0.419N     P=0.403N     P=0.401N   |  P=0.246N     P=0.295N     P=0.297N     P=0.297N   |
|COCHRAN-ARMITAGE       |  P=0.361N                                          |  P=0.242N                                          |
|FISHER EXACT           |               P=0.414N     P=0.420N     P=0.401N   |               P=0.288N     P=0.304N     P=0.299N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE  14
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Tooth                                                                                                                            |
|     Odontoma                                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/67 (0%)    1/77 (1%)    2/76 (3%)    1/79 (1%)  |  0/74 (0%)    0/76 (0%)    0/73 (0%)    1/74 (1%)  |
|ADJUSTED (b)           |   0.0%         4.3%         6.9%         4.3%      |   0.0%         0.0%         0.0%         2.6%      |
|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)|  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)           |  0/19 (0%)    1/23 (4%)    2/29 (7%)    1/23 (4%)  |  0/41 (0%)    0/40 (0%)    0/42 (0%)    1/38 (3%)  |
|FIRST INCIDENCE (DAYS) |   ---          737 (T)      737 (T)      737 (T)   |   ---          ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.410      P=0.538      P=0.335      P=0.538    |  P=0.188        (e)          (e)        P=0.485    |
|INCIDENTAL TUMOR       |  P=0.410      P=0.538      P=0.335      P=0.538    |  P=0.188        (e)          (e)        P=0.485    |
|LOGISTIC REGRESSION    |  P=0.410      P=0.538      P=0.335      P=0.538    |  P=0.188        (e)          (e)        P=0.485    |
|COCHRAN-ARMITAGE       |  P=0.405                                           |  P=0.196                                           |
|FISHER EXACT           |               P=0.535      P=0.281      P=0.541    |                 (e)          (e)        P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  0/74 (0%)    3/76 (4%)    1/73 (1%)    1/74 (1%)  |
|ADJUSTED (b)           |                                                    |   0.0%         6.9%         2.3%         2.6%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  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%)   |
|TERMINAL (d)           |                                                    |  0/41 (0%)    2/40 (5%)    0/42 (0%)    1/38 (3%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   ---          657          681          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.583      P=0.125      P=0.487      P=0.485    |
|INCIDENTAL TUMOR       |                                                    |  P=0.603N     P=0.164      P=0.536      P=0.485    |
|LOGISTIC REGRESSION    |                                                    |  P=0.599      P=0.135      P=0.501      P=0.485    |
|COCHRAN-ARMITAGE       |                                                    |  P=0.595                                           |
|FISHER EXACT           |                                                    |               P=0.128      P=0.497      P=0.500    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE  15
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  2/74 (3%)    4/76 (5%)    0/73 (0%)    1/74 (1%)  |
|ADJUSTED (b)           |                                                    |   4.3%         8.3%         0.0%         2.6%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  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%)   |
|TERMINAL (d)           |                                                    |  1/41 (2%)    2/40 (5%)    0/42 (0%)    1/38 (3%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   559          583          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.204N     P=0.361      P=0.235N     P=0.513N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.228N     P=0.357      P=0.268N     P=0.533N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.191N     P=0.370      P=0.238N     P=0.486N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.198N                                          |
|FISHER EXACT           |                                                    |               P=0.353      P=0.252N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Sarcoma Stromal or Polyp Stromal                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  3/74 (4%)    4/76 (5%)    1/73 (1%)    1/74 (1%)  |
|ADJUSTED (b)           |                                                    |   6.7%         8.3%         2.4%         2.6%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  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%)   |
|TERMINAL (d)           |                                                    |  2/41 (5%)    2/40 (5%)    1/42 (2%)    1/38 (3%)  |
|FIRST INCIDENCE (DAYS) |                                                    |   559          583          729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.145N     P=0.519      P=0.299N     P=0.324N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.162N     P=0.520      P=0.326N     P=0.339N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.132N     P=0.541      P=0.304N     P=0.292N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.138N                                          |
|FISHER EXACT           |                                                    |               P=0.515      P=0.315N     P=0.310N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE  16
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma                                                                                                             |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/67 (4%)    2/77 (3%)    2/76 (3%)    3/79 (4%)  |  3/74 (4%)    6/76 (8%)    8/73 (11%)   4/74 (5%)  |
|ADJUSTED (b)           |  10.3%         5.7%         6.9%         8.3%      |   7.1%        13.2%        17.3%         8.7%      |
|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)           |  1/19 (5%)    0/23 (0%)    2/29 (7%)    0/23 (0%)  |  2/41 (5%)    3/40 (8%)    5/42 (12%)   1/38 (3%)  |
|FIRST INCIDENCE (DAYS) |   559          604          737 (T)      271       |   728          640          538          640       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.545N     P=0.404N     P=0.343N     P=0.553N   |  P=0.459      P=0.249      P=0.112      P=0.483    |
|INCIDENTAL TUMOR       |  P=0.578      P=0.531N     P=0.582N     P=0.599N   |  P=0.523N     P=0.378      P=0.145      P=0.629    |
|LOGISTIC REGRESSION    |  P=0.555N     P=0.428N     P=0.379N     P=0.578N   |  P=0.492      P=0.280      P=0.103      P=0.518    |
|COCHRAN-ARMITAGE       |  P=0.569N                                          |  P=0.479                                           |
|FISHER EXACT           |               P=0.434N     P=0.440N     P=0.578N   |               P=0.261      P=0.100      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/67 (4%)    2/77 (3%)    2/76 (3%)    4/79 (5%)  |  3/74 (4%)    6/76 (8%)    9/73 (12%)   5/74 (7%)  |
|ADJUSTED (b)           |  10.3%         5.7%         6.9%        11.0%      |   7.1%        13.2%        18.9%        11.2%      |
|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%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  1/19 (5%)    0/23 (0%)    2/29 (7%)    0/23 (0%)  |  2/41 (5%)    3/40 (8%)    5/42 (12%)   2/38 (5%)  |
|FIRST INCIDENCE (DAYS) |   559          604          737 (T)      271       |   728          640          538          640       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.453      P=0.404N     P=0.343N     P=0.633    |  P=0.320      P=0.249      P=0.073      P=0.340    |
|INCIDENTAL TUMOR       |  P=0.411      P=0.531N     P=0.582N     P=0.603    |  P=0.438      P=0.378      P=0.087      P=0.467    |
|LOGISTIC REGRESSION    |  P=0.434      P=0.428N     P=0.379N     P=0.598    |  P=0.350      P=0.280      P=0.065      P=0.373    |
|COCHRAN-ARMITAGE       |  P=0.419                                           |  P=0.337                                           |
|FISHER EXACT           |               P=0.434N     P=0.440N     P=0.591    |               P=0.261      P=0.062      P=0.359    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE  17
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Histiocytic Sarcoma                                                                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/67 (0%)    0/77 (0%)    0/76 (0%)    1/79 (1%)  |  2/74 (3%)    0/76 (0%)    0/73 (0%)    2/74 (3%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         1.5%      |   4.9%         0.0%         0.0%         3.5%      |
|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)           |  0/19 (0%)    0/23 (0%)    0/29 (0%)    0/23 (0%)  |  2/41 (5%)    0/40 (0%)    0/42 (0%)    0/38 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          422       |   729 (T)      ---          ---          495       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.214        (e)          (e)        P=0.539    |  P=0.489      P=0.244N     P=0.233N     P=0.690    |
|INCIDENTAL TUMOR       |  P=0.227        (e)          (e)        P=0.602    |  P=0.601      P=0.244N     P=0.233N     P=0.591N   |
|LOGISTIC REGRESSION    |  P=0.207        (e)          (e)        P=0.523    |  P=0.496      P=0.244N     P=0.233N     P=0.685N   |
|COCHRAN-ARMITAGE       |  P=0.211                                           |  P=0.491                                           |
|FISHER EXACT           |                 (e)          (e)        P=0.541    |               P=0.242N     P=0.252N     P=0.690N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma And Histiocytic Sarcoma                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/67 (3%)    2/77 (3%)    2/76 (3%)    6/79 (8%)  | 15/74 (20%)  12/76 (16%)   9/73 (12%)   9/74 (12%) |
|ADJUSTED (b)           |   6.5%         4.5%         6.9%        14.0%      |  33.1%        25.3%        18.5%        18.6%      |
|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)|  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)           |  0/19 (0%)    0/23 (0%)    2/29 (7%)    1/23 (4%)  | 11/41 (27%)   6/40 (15%)   5/42 (12%)   4/38 (11%) |
|FIRST INCIDENCE (DAYS) |   590          501          737 (T)      137       |   618          597          321          426       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.093      P=0.626N     P=0.558N     P=0.243    |  P=0.129N     P=0.347N     P=0.130N     P=0.167N   |
|INCIDENTAL TUMOR       |  P=0.089      P=0.613N     P=0.669N     P=0.221    |  P=0.071N     P=0.171N     P=0.128N     P=0.063N   |
|LOGISTIC REGRESSION    |  P=0.078      P=0.641N     P=0.590N     P=0.196    |  P=0.090N     P=0.252N     P=0.125N     P=0.106N   |
|COCHRAN-ARMITAGE       |  P=0.077                                           |  P=0.105N                                          |
|FISHER EXACT           |               P=0.636N     P=0.641N     P=0.198    |               P=0.308N     P=0.140N     P=0.132N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE  18
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Lymphoma: Histiocytic, Lymphocytic, Mixed, NOS, or Undifferentiated                                               |
|     Cell Type                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/67 (3%)    2/77 (3%)    2/76 (3%)    5/79 (6%)  | 13/74 (18%)  12/76 (16%)   9/73 (12%)   7/74 (9%)  |
|ADJUSTED (b)           |   6.5%         4.5%         6.9%        12.7%      |  28.6%        25.3%        18.5%        15.7%      |
|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)           |  0/19 (0%)    0/23 (0%)    2/29 (7%)    1/23 (4%)  |  9/41 (22%)   6/40 (15%)   5/42 (12%)   4/38 (11%) |
|FIRST INCIDENCE (DAYS) |   590          501          737 (T)      137       |   618          597          321          426       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.176      P=0.626N     P=0.558N     P=0.344    |  P=0.096N     P=0.506N     P=0.240N     P=0.146N   |
|INCIDENTAL TUMOR       |  P=0.165      P=0.613N     P=0.669N     P=0.300    |  P=0.060N     P=0.299N     P=0.241N     P=0.068N   |
|LOGISTIC REGRESSION    |  P=0.154      P=0.641N     P=0.590N     P=0.293    |  P=0.066N     P=0.413N     P=0.236N     P=0.094N   |
|COCHRAN-ARMITAGE       |  P=0.151                                           |  P=0.077N                                          |
|FISHER EXACT           |               P=0.636N     P=0.641N     P=0.294    |               P=0.471N     P=0.255N     P=0.114N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 22/67 (33%)  17/77 (22%)  29/76 (38%)  26/79 (33%) | 21/74 (28%)  28/76 (37%)  29/73 (40%)  24/74 (32%) |
|ADJUSTED (b)           |  72.6%        49.0%        63.4%        67.1%      |  44.5%        55.7%        56.6%        53.0%      |
|INTERIM SACRIFICE 1 (c)|  2/5 (40%)    0/5 (0%)     2/5 (40%)    0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  2/5 (40%)    1/5 (20%)    2/5 (40%)    0/5 (0%)   |  0/5 (0%)     1/5 (20%)    1/5 (20%)    0/5 (0%)   |
|TERMINAL (d)           | 12/19 (63%)   8/23 (35%)  15/29 (52%)  12/23 (52%) | 16/41 (39%)  19/40 (48%)  20/42 (48%)  17/38 (45%) |
|FIRST INCIDENCE (DAYS) |   199 (I)      458 (I)      199 (I)      431       |    92          162          459 (I)      619       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.345      P=0.083N     P=0.478N     P=0.502N   |  P=0.336      P=0.150      P=0.131      P=0.277    |
|INCIDENTAL TUMOR       |  P=0.344      P=0.077N     P=0.513      P=0.498N   |  P=0.375      P=0.176      P=0.106      P=0.368    |
|LOGISTIC REGRESSION    |  P=0.323      P=0.082N     P=0.425      P=0.515N   |  P=0.447      P=0.234      P=0.106      P=0.305    |
|COCHRAN-ARMITAGE       |  P=0.280                                           |  P=0.402                                           |
|FISHER EXACT           |               P=0.104N     P=0.313      P=0.567    |               P=0.176      P=0.101      P=0.361    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE  19
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   O MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |   0 MG/M3      1.25MGM3     2.5MG/M3     5.0MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 16/67 (24%)  29/77 (38%)  23/76 (30%)  30/79 (38%) | 30/74 (41%)  37/76 (49%)  28/73 (38%)  28/74 (38%) |
|ADJUSTED (b)           |  44.2%        61.2%        53.7%        61.7%      |  61.0%        64.6%        51.0%        49.8%      |
|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)|  1/5 (20%)    1/5 (20%)    1/5 (20%)    0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  4/19 (21%)   7/23 (30%)  12/29 (41%)   8/23 (35%) | 22/41 (54%)  20/40 (50%)  16/42 (38%)  11/38 (29%) |
|FIRST INCIDENCE (DAYS) |   392          341          458 (I)      137       |   586          469          321          426       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.180      P=0.115      P=0.525      P=0.107    |  P=0.315N     P=0.192      P=0.410N     P=0.503N   |
|INCIDENTAL TUMOR       |  P=0.110      P=0.054      P=0.267      P=0.046 *  |  P=0.079N     P=0.450      P=0.394N     P=0.139N   |
|LOGISTIC REGRESSION    |  P=0.106      P=0.042 *    P=0.354      P=0.054    |  P=0.135N     P=0.396      P=0.413N     P=0.245N   |
|COCHRAN-ARMITAGE       |  P=0.103                                           |  P=0.244N                                          |
|FISHER EXACT           |               P=0.054      P=0.253      P=0.049 *  |               P=0.201      P=0.459N     P=0.433N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 34/67 (51%)  39/77 (51%)  45/76 (59%)  44/79 (56%) | 37/74 (50%)  50/76 (66%)  46/73 (63%)  40/74 (54%) |
|ADJUSTED (b)           |  85.0%        76.6%        86.8%        81.4%      |  70.7%        80.6%        77.9%        72.1%      |
|INTERIM SACRIFICE 1 (c)|  2/5 (40%)    0/5 (0%)     2/5 (40%)    0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|INTERIM SACRIFICE 2 (c)|  3/5 (60%)    2/5 (40%)    3/5 (60%)    0/5 (0%)   |  0/5 (0%)     1/5 (20%)    1/5 (20%)    0/5 (0%)   |
|TERMINAL (d)           | 14/19 (74%)  12/23 (52%)  23/29 (79%)  14/23 (61%) | 26/41 (63%)  28/40 (70%)  29/42 (69%)  23/38 (61%) |
|FIRST INCIDENCE (DAYS) |   199 (I)      341          199 (I)      137       |    92          162          321          426       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.377      P=0.471N     P=0.465N     P=0.451    |  P=0.449      P=0.051      P=0.142      P=0.300    |
|INCIDENTAL TUMOR       |  P=0.299      P=0.539N     P=0.355      P=0.382    |  P=0.356N     P=0.083      P=0.067      P=0.571    |
|LOGISTIC REGRESSION    |  P=0.288      P=0.540N     P=0.327      P=0.373    |  P=0.423N     P=0.067      P=0.080      P=0.498    |
|COCHRAN-ARMITAGE       |  P=0.245                                           |  P=0.530                                           |
|FISHER EXACT           |               P=0.562N     P=0.198      P=0.333    |               P=0.036 *    P=0.077      P=0.371    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 06                                                 PAGE  20
                                STATISTICAL ANALYSIS OF PRIMARY TUMORS IN MICE(B6C3F1) -- NICKEL OXIDE
                                                 MALE TERMINAL SACRIFICE AT 106 WEEKS
                                                 FEMALE 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).