National Toxicology Program

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TDMS Study 05123-05 Pathology Tables

NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: LITRI                                                    NICKEL OXIDE                                     DATE: 05/20/95       
EXPERIMENT: 05123 TEST: 05                                                                                     TIME: 04:50:32       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: Y01-ES-30108                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C00862       
PATHOLOGIST: P. HALEY                                                                                          CAS: 001313991       
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: LITRI                                                    NICKEL OXIDE                                     DATE: 05/20/95       
EXPERIMENT: 05123 TEST: 05                                                                                     TIME: 04:50:32       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: Y01-ES-30108                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C00862       
PATHOLOGIST: P. HALEY                                                                                          CAS: 001313991       


                                                    RATS(FISCHER344)
                                              ----------------------------
             FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
             IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.
                                                                    
                                                    ----------------
                                                    Adrenal Cortex
                                                    Adrenal Medulla
                                                    Bone Marrow
                                                    Brain
                                                    Clitoral Gland
                                                    Clitoral/Preputial Gland
                                                    Epididymis
                                                    Heart
                                                    Islets, Pancreatic
                                                    Kidney
                                                    Larynx
                                                    Liver
                                                    Lung
                                                    Nose
                                                    Ovary
                                                    Pancreas
                                                    Parathyroid Gland
                                                    Pituitary Gland
                                                    Preputial Gland
                                                    Prostate
                                                    Salivary Glands
                                                    Spleen
                                                    Testes
                                                    Thymus
                                                    Thyroid Gland
                                                    Urinary Bladder
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: LITRI                                                    NICKEL OXIDE                                     DATE: 05/20/95       
EXPERIMENT: 05123 TEST: 05                                                                                     TIME: 04:50:32       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: Y01-ES-30108                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C00862       
PATHOLOGIST: P. HALEY                                                                                          CAS: 001313991       


                                     SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
                                          IN THE ANALYSIS OF THE STUDY OF NICKEL OXIDE
              ====================================================================================================
                                                           MALE RATS
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------
              Adrenal Medulla               Pheochromocytoma Benign
                                            Pheochromocytoma Malignant
                                            Pheochromocytoma: Benign, Complex, Malignant, NOS
              Lung                          Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
              Pituitary Gland: Pars Distalis or Unspecified Site
                                            Adenoma
                                            Carcinoma or Adenoma
              Testes                        Adenoma
              Thyroid Gland: C-Cell         Carcinoma or Adenoma
              ====================================================================================================
                                                           FEMALE RATS
                                                          -------------
                  ORGAN                               MORPHOLOGY
                 -------                             ------------
              Adrenal Medulla               Pheochromocytoma Benign
                                            Pheochromocytoma: Benign, Complex, Malignant, NOS
              Lung                          Alveolar/Bronchiolar Adenoma
                                            Alveolar/Bronchiolar Carcinoma
                                            Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma
              Skin                          Basal or Sq. Cell Carcinoma, Carcinoma, Basosq. Tumor (M or B), Basal
                                             Cell Adenoma, Adenoma, Papilloma, Sq Papilloma, Keratoacanthoma, Trichoepithelioma
              Uterus                        Polyp Stromal
              ====================================================================================================
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE   1
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Benign                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 27/59 (46%)  24/57 (42%)  28/58 (48%)  32/57 (56%) |  4/56 (7%)    7/57 (12%)   6/57 (11%)  18/58 (31%) |
|ADJUSTED (b)           |  81.8%        69.3%        83.7%        93.8%      |  15.1%        21.1%        22.0%        56.5%      |
|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%)     2/5 (40%)    0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/4 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  9/14 (64%)   6/15 (40%)  10/15 (67%)  10/12 (83%) |  2/21 (10%)   3/25 (12%)   2/20 (10%)  13/26 (50%) |
|FIRST INCIDENCE (DAYS) |   475          570          459 (I)      553       |   558          524          611          519       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.053      P=0.302N     P=0.528      P=0.123    |  P<0.001 **   P=0.350      P=0.353      P=0.003 ** |
|INCIDENTAL TUMOR       |  P=0.057      P=0.362N     P=0.516      P=0.127    |  P<0.001 **   P=0.296      P=0.369      P=0.002 ** |
|LOGISTIC REGRESSION    |  P=0.041 *    P=0.334N     P=0.439      P=0.090    |  P<0.001 **   P=0.297      P=0.381      P=0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.100                                           |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.417N     P=0.465      P=0.176    |               P=0.274      P=0.382      P=0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma Malignant                                                                                                  |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/59 (0%)    0/57 (0%)    1/58 (2%)    6/57 (11%) |  0/56 (0%)    0/57 (0%)    0/57 (0%)    0/58 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         2.8%        33.9%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/4 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/14 (0%)    0/15 (0%)    0/15 (0%)    3/12 (25%) |  0/21 (0%)    0/25 (0%)    0/20 (0%)    0/26 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          619          467       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P<0.001 **     (e)        P=0.484      P=0.013 *  |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P<0.001 **     (e)        P=0.453      P=0.018 *  |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P<0.001 **     (e)        P=0.497      P=0.015 *  |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P<0.001 **                                        |    (e)                                             |
|FISHER EXACT           |                 (e)        P=0.496      P=0.012 *  |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE   2
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Pheochromocytoma: Benign, Complex, Malignant, NOS                                                                           |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 27/59 (46%)  24/57 (42%)  29/58 (50%)  35/57 (61%) |  4/56 (7%)    7/57 (12%)   6/57 (11%)  18/58 (31%) |
|ADJUSTED (b)           |  81.8%        69.3%        84.2%        97.0%      |  15.1%        21.1%        22.0%        56.5%      |
|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%)     2/5 (40%)    0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/4 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  9/14 (64%)   6/15 (40%)  10/15 (67%)  11/12 (92%) |  2/21 (10%)   3/25 (12%)   2/20 (10%)  13/26 (50%) |
|FIRST INCIDENCE (DAYS) |   475          570          459 (I)      467       |   558          524          611          519       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.017 *    P=0.302N     P=0.464      P=0.055    |  P<0.001 **   P=0.350      P=0.353      P=0.003 ** |
|INCIDENTAL TUMOR       |  P=0.012 *    P=0.362N     P=0.427      P=0.040 *  |  P<0.001 **   P=0.296      P=0.369      P=0.002 ** |
|LOGISTIC REGRESSION    |  P=0.008 **   P=0.334N     P=0.360      P=0.026 *  |  P<0.001 **   P=0.297      P=0.381      P=0.001 ** |
|COCHRAN-ARMITAGE       |  P=0.028 *                                         |  P<0.001 **                                        |
|FISHER EXACT           |               P=0.417N     P=0.392      P=0.066    |               P=0.274      P=0.382      P=0.001 ** |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/59 (2%)    3/58 (5%)    2/58 (3%)    2/56 (4%)  |  1/58 (2%)    5/58 (9%)    2/56 (4%)    0/55 (0%)  |
|ADJUSTED (b)           |   5.0%        11.2%         6.4%         4.7%      |   4.8%        16.2%        10.0%         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)           |  0/14 (0%)    1/15 (7%)    0/15 (0%)    0/12 (0%)  |  1/21 (5%)    3/26 (12%)   2/20 (10%)   0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   705          595          578          570       |   729 (T)      537          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.455      P=0.319      P=0.496      P=0.472    |  P=0.151N     P=0.145      P=0.483      P=0.473N   |
|INCIDENTAL TUMOR       |  P=0.481      P=0.248      P=0.473      P=0.467    |  P=0.151N     P=0.183      P=0.483      P=0.473N   |
|LOGISTIC REGRESSION    |  P=0.487      P=0.308      P=0.492      P=0.481    |  P=0.183N     P=0.117      P=0.483      P=0.473N   |
|COCHRAN-ARMITAGE       |  P=0.487                                           |  P=0.175N                                          |
|FISHER EXACT           |               P=0.303      P=0.494      P=0.480    |               P=0.103      P=0.487      P=0.513N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE   3
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/59 (0%)    0/58 (0%)    1/58 (2%)    1/56 (2%)  |  2/58 (3%)    0/58 (0%)    0/56 (0%)    1/55 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         2.4%         2.0%      |   5.3%         0.0%         0.0%         2.5%      |
|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)           |  0/14 (0%)    0/15 (0%)    0/15 (0%)    0/12 (0%)  |  0/21 (0%)    0/26 (0%)    0/20 (0%)    0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          578          475       |   594          ---          ---          607       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.234        (e)        P=0.491      P=0.488    |  P=0.496N     P=0.222N     P=0.247N     P=0.511N   |
|INCIDENTAL TUMOR       |  P=0.259        (e)        P=0.453      P=0.581    |  P=0.531N     P=0.329N     P=0.275N     P=0.612N   |
|LOGISTIC REGRESSION    |  P=0.216        (e)        P=0.500      P=0.415    |  P=0.490N     P=0.243N     P=0.245N     P=0.515N   |
|COCHRAN-ARMITAGE       |  P=0.236                                           |  P=0.496N                                          |
|FISHER EXACT           |                 (e)        P=0.496      P=0.487    |               P=0.248N     P=0.257N     P=0.520N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral/Preputial Gland                                                                                                         |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/59 (2%)    3/58 (5%)    2/58 (3%)    3/56 (5%)  |  3/58 (5%)    5/58 (9%)    2/56 (4%)    1/55 (2%)  |
|ADJUSTED (b)           |   5.0%        11.2%         6.4%         6.6%      |   9.8%        16.2%        10.0%         2.5%      |
|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)           |  0/14 (0%)    1/15 (7%)    0/15 (0%)    0/12 (0%)  |  1/21 (5%)    3/26 (12%)   2/20 (10%)   0/24 (0%)  |
|FIRST INCIDENCE (DAYS) |   705          595          578          475       |   594          537          729 (T)      607       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.262      P=0.319      P=0.496      P=0.282    |  P=0.136N     P=0.436      P=0.519N     P=0.305N   |
|INCIDENTAL TUMOR       |  P=0.296      P=0.248      P=0.473      P=0.317    |  P=0.147N     P=0.423      P=0.542N     P=0.382N   |
|LOGISTIC REGRESSION    |  P=0.289      P=0.308      P=0.492      P=0.274    |  P=0.159N     P=0.377      P=0.522N     P=0.326N   |
|COCHRAN-ARMITAGE       |  P=0.286                                           |  P=0.153N                                          |
|FISHER EXACT           |               P=0.303      P=0.494      P=0.290    |               P=0.358      P=0.517N     P=0.329N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE   4
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/59 (3%)    3/58 (5%)    2/58 (3%)    2/57 (4%)  |  1/57 (2%)    1/58 (2%)    1/58 (2%)    0/59 (0%)  |
|ADJUSTED (b)           |  11.8%        15.7%        11.1%         9.4%      |   4.8%         3.0%         5.0%         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)           |  1/14 (7%)    1/15 (7%)    1/15 (7%)    0/12 (0%)  |  1/21 (5%)    0/26 (0%)    1/20 (5%)    0/26 (0%)  |
|FIRST INCIDENCE (DAYS) |   705          686          706          671       |   729 (T)      703          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.591      P=0.525      P=0.662N     P=0.636    |  P=0.292N     P=0.718N     P=0.752      P=0.457N   |
|INCIDENTAL TUMOR       |  P=0.552N     P=0.560      P=0.682N     P=0.693N   |  P=0.317N     P=0.737N     P=0.752      P=0.457N   |
|LOGISTIC REGRESSION    |  P=0.596N     P=0.533      P=0.696N     P=0.654    |  P=0.312N     P=0.740N     P=0.752      P=0.457N   |
|COCHRAN-ARMITAGE       |  P=0.540N                                          |  P=0.307N                                          |
|FISHER EXACT           |               P=0.492      P=0.684      P=0.678    |               P=0.748N     P=0.748N     P=0.491N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/59 (2%)    1/58 (2%)    2/58 (3%)    0/57 (0%)  |  0/57 (0%)    0/58 (0%)    0/58 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   7.1%         4.8%         9.1%         0.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  1/14 (7%)    0/15 (0%)    1/15 (7%)    0/12 (0%)  |  0/21 (0%)    0/26 (0%)    0/20 (0%)    0/26 (0%)  |
|FIRST INCIDENCE (DAYS) |   733 (T)      704          606          ---       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.397N     P=0.747N     P=0.516      P=0.531N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.389N     P=0.734N     P=0.489      P=0.531N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.392N     P=0.748N     P=0.493      P=0.531N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.370N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.748      P=0.494      P=0.509N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE   5
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/59 (5%)    4/58 (7%)    4/58 (7%)    2/57 (4%)  |  1/57 (2%)    1/58 (2%)    1/58 (2%)    0/59 (0%)  |
|ADJUSTED (b)           |  18.6%        19.8%        19.6%         9.4%      |   4.8%         3.0%         5.0%         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)           |  2/14 (14%)   1/15 (7%)    2/15 (13%)   0/12 (0%)  |  1/21 (5%)    0/26 (0%)    1/20 (5%)    0/26 (0%)  |
|FIRST INCIDENCE (DAYS) |   705          686          606          671       |   729 (T)      703          729 (T)      ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.446N     P=0.530      P=0.537      P=0.569N   |  P=0.292N     P=0.718N     P=0.752      P=0.457N   |
|INCIDENTAL TUMOR       |  P=0.398N     P=0.570      P=0.503      P=0.512N   |  P=0.317N     P=0.737N     P=0.752      P=0.457N   |
|LOGISTIC REGRESSION    |  P=0.435N     P=0.541      P=0.495      P=0.559N   |  P=0.312N     P=0.740N     P=0.752      P=0.457N   |
|COCHRAN-ARMITAGE       |  P=0.380N                                          |  P=0.307N                                          |
|FISHER EXACT           |               P=0.490      P=0.490      P=0.516N   |               P=0.748N     P=0.748N     P=0.491N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Adenoma                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/59 (5%)    6/58 (10%)   3/59 (5%)    2/57 (4%)  |  0/59 (0%)    1/58 (2%)    0/58 (0%)    1/59 (2%)  |
|ADJUSTED (b)           |  11.2%        25.0%         8.9%        12.0%      |   0.0%         3.8%         0.0%         3.8%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/1 (0%)     0/0        |  0/1 (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)           |  1/14 (7%)    2/15 (13%)   0/15 (0%)    1/12 (8%)  |  0/21 (0%)    1/26 (4%)    0/20 (0%)    1/26 (4%)  |
|FIRST INCIDENCE (DAYS) |   475          670          567          665       |   ---          729 (T)      ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.347N     P=0.283      P=0.634      P=0.555N   |  P=0.440      P=0.543        (e)        P=0.543    |
|INCIDENTAL TUMOR       |  P=0.272N     P=0.300      P=0.644      P=0.488N   |  P=0.440      P=0.543        (e)        P=0.543    |
|LOGISTIC REGRESSION    |  P=0.285N     P=0.250      P=0.659N     P=0.520N   |  P=0.440      P=0.543        (e)        P=0.543    |
|COCHRAN-ARMITAGE       |  P=0.269N                                          |  P=0.410                                           |
|FISHER EXACT           |               P=0.237      P=0.660N     P=0.516N   |               P=0.496        (e)        P=0.500    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE   6
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma                                                                                                    |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/59 (3%)    1/58 (2%)    2/59 (3%)    1/57 (2%)  |  0/59 (0%)    0/58 (0%)    0/58 (0%)    0/59 (0%)  |
|ADJUSTED (b)           |   6.2%         6.7%         8.7%         8.3%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/1 (0%)     0/0        |  0/1 (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)           |  0/14 (0%)    1/15 (7%)    1/15 (7%)    1/12 (8%)  |  0/21 (0%)    0/26 (0%)    0/20 (0%)    0/26 (0%)  |
|FIRST INCIDENCE (DAYS) |   628          733 (T)      564          733 (T)   |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.498N     P=0.459N     P=0.687      P=0.532N   |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.490N     P=0.598N     P=0.637      P=0.558N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.474N     P=0.497N     P=0.691      P=0.521N   |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.457N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.506N     P=0.691N     P=0.513N   |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma or Hepatocellular Adenoma                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/59 (8%)    7/58 (12%)   5/59 (8%)    2/57 (4%)  |  0/59 (0%)    1/58 (2%)    0/58 (0%)    1/59 (2%)  |
|ADJUSTED (b)           |  16.7%        30.8%        16.8%        12.0%      |   0.0%         3.8%         0.0%         3.8%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/1 (0%)     0/0        |  0/1 (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)           |  1/14 (7%)    3/15 (20%)   1/15 (7%)    1/12 (8%)  |  0/21 (0%)    1/26 (4%)    0/20 (0%)    1/26 (4%)  |
|FIRST INCIDENCE (DAYS) |   475          670          564          665       |   ---          729 (T)      ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.185N     P=0.439      P=0.602      P=0.268N   |  P=0.440      P=0.543        (e)        P=0.543    |
|INCIDENTAL TUMOR       |  P=0.137N     P=0.389      P=0.575      P=0.231N   |  P=0.440      P=0.543        (e)        P=0.543    |
|LOGISTIC REGRESSION    |  P=0.138N     P=0.388      P=0.630N     P=0.234N   |  P=0.440      P=0.543        (e)        P=0.543    |
|COCHRAN-ARMITAGE       |  P=0.128N                                          |  P=0.410                                           |
|FISHER EXACT           |               P=0.369      P=0.629N     P=0.234N   |               P=0.496        (e)        P=0.500    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE   7
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatocellular Carcinoma, Hepatocellular Adenoma, or Hepatoblastoma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  5/59 (8%)    7/58 (12%)   5/59 (8%)    2/57 (4%)  |  0/59 (0%)    1/58 (2%)    0/58 (0%)    1/59 (2%)  |
|ADJUSTED (b)           |  16.7%        30.8%        16.8%        12.0%      |   0.0%         3.8%         0.0%         3.8%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/1 (0%)     0/0        |  0/1 (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)           |  1/14 (7%)    3/15 (20%)   1/15 (7%)    1/12 (8%)  |  0/21 (0%)    1/26 (4%)    0/20 (0%)    1/26 (4%)  |
|FIRST INCIDENCE (DAYS) |   475          670          564          665       |   ---          729 (T)      ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.185N     P=0.439      P=0.602      P=0.268N   |  P=0.440      P=0.543        (e)        P=0.543    |
|INCIDENTAL TUMOR       |  P=0.137N     P=0.389      P=0.575      P=0.231N   |  P=0.440      P=0.543        (e)        P=0.543    |
|LOGISTIC REGRESSION    |  P=0.138N     P=0.388      P=0.630N     P=0.234N   |  P=0.440      P=0.543        (e)        P=0.543    |
|COCHRAN-ARMITAGE       |  P=0.128N                                          |  P=0.410                                           |
|FISHER EXACT           |               P=0.369      P=0.629N     P=0.234N   |               P=0.496        (e)        P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Adenoma                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/65 (0%)    1/65 (2%)    3/65 (5%)    2/64 (3%)  |  1/65 (2%)    0/65 (0%)    1/65 (2%)    4/65 (6%)  |
|ADJUSTED (b)           |   0.0%         2.6%        20.0%        11.4%      |   4.8%         0.0%         3.1%        15.4%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  0/14 (0%)    0/15 (0%)    3/15 (20%)   1/12 (8%)  |  1/21 (5%)    0/26 (0%)    0/20 (0%)    4/26 (15%) |
|FIRST INCIDENCE (DAYS) |   ---          623          733 (T)      633       |   729 (T)      ---          655          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.135      P=0.516      P=0.128      P=0.223    |  P=0.044 *    P=0.457N     P=0.748      P=0.245    |
|INCIDENTAL TUMOR       |  P=0.139      P=0.408      P=0.128      P=0.205    |  P=0.038 *    P=0.457N     P=0.755      P=0.245    |
|LOGISTIC REGRESSION    |  P=0.139      P=0.501      P=0.128      P=0.218    |  P=0.032 *    P=0.457N     P=0.758      P=0.245    |
|COCHRAN-ARMITAGE       |  P=0.170                                           |  P=0.034 *                                         |
|FISHER EXACT           |               P=0.500      P=0.122      P=0.244    |               P=0.500N     P=0.752N     P=0.183    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE   8
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma                                                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/65 (0%)    0/65 (0%)    3/65 (5%)    2/64 (3%)  |  0/65 (0%)    0/65 (0%)    5/65 (8%)    1/65 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         9.6%        13.2%      |   0.0%         0.0%        22.3%         3.8%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  0/14 (0%)    0/15 (0%)    0/15 (0%)    1/12 (8%)  |  0/21 (0%)    0/26 (0%)    4/20 (20%)   1/26 (4%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          567          697       |   ---          ---          643          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.070        (e)        P=0.121      P=0.203    |  P=0.302        (e)        P=0.029 *    P=0.543    |
|INCIDENTAL TUMOR       |  P=0.097        (e)        P=0.108      P=0.229    |  P=0.304        (e)        P=0.026 *    P=0.543    |
|LOGISTIC REGRESSION    |  P=0.089        (e)        P=0.118      P=0.206    |  P=0.262        (e)        P=0.030 *    P=0.543    |
|COCHRAN-ARMITAGE       |  P=0.102                                           |  P=0.266                                           |
|FISHER EXACT           |                 (e)        P=0.122      P=0.244    |                 (e)        P=0.029 *    P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Alveolar/Bronchiolar Carcinoma or Alveolar/Bronchiolar Adenoma                                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/65 (0%)    1/65 (2%)    6/65 (9%)    4/64 (6%)  |  1/65 (2%)    0/65 (0%)    6/65 (9%)    5/65 (8%)  |
|ADJUSTED (b)           |   0.0%         2.6%        27.7%        23.7%      |   4.8%         0.0%        24.7%        19.2%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  0/14 (0%)    0/15 (0%)    3/15 (20%)   2/12 (17%) |  1/21 (5%)    0/26 (0%)    4/20 (20%)   5/26 (19%) |
|FIRST INCIDENCE (DAYS) |   ---          623          567          633       |   729 (T)      ---          643          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.020 *    P=0.516      P=0.020 *    P=0.050 *  |  P=0.035 *    P=0.457N     P=0.051      P=0.152    |
|INCIDENTAL TUMOR       |  P=0.028 *    P=0.408      P=0.018 *    P=0.052    |  P=0.032 *    P=0.457N     P=0.048 *    P=0.152    |
|LOGISTIC REGRESSION    |  P=0.025 *    P=0.501      P=0.016 *    P=0.048 *  |  P=0.022 *    P=0.457N     P=0.052      P=0.152    |
|COCHRAN-ARMITAGE       |  P=0.036 *                                         |  P=0.025 *                                         |
|FISHER EXACT           |               P=0.500      P=0.014 *    P=0.058    |               P=0.500N     P=0.057      P=0.104    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE   9
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/65 (0%)    0/65 (0%)    0/65 (0%)    0/64 (0%)  |  1/65 (2%)    0/65 (0%)    3/65 (5%)    1/65 (2%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   4.8%         0.0%        12.6%         2.1%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  0/14 (0%)    0/15 (0%)    0/15 (0%)    0/12 (0%)  |  1/21 (5%)    0/26 (0%)    2/20 (10%)   0/26 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   729 (T)      ---          643          538       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.511      P=0.457N     P=0.290      P=0.737N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.540      P=0.457N     P=0.271      P=0.642N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.483      P=0.457N     P=0.293      P=0.761N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.485                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.500N     P=0.310      P=0.752N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/65 (0%)    0/65 (0%)    0/65 (0%)    0/64 (0%)  |  2/65 (3%)    1/65 (2%)    4/65 (6%)    2/65 (3%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   9.5%         3.8%        14.7%         5.8%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  0/14 (0%)    0/15 (0%)    0/15 (0%)    0/12 (0%)  |  2/21 (10%)   1/26 (4%)    2/20 (10%)   1/26 (4%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   729 (T)      729 (T)      611          538       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.525      P=0.425N     P=0.323      P=0.636N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.548      P=0.425N     P=0.286      P=0.558N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.485      P=0.425N     P=0.325      P=0.691N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.489                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.500N     P=0.340      P=0.690N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE  10
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroadenoma                                                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/65 (3%)    0/65 (0%)    1/65 (2%)    0/64 (0%)  | 12/65 (18%)  14/65 (22%)  15/65 (23%)  12/65 (18%) |
|ADJUSTED (b)           |  14.3%         0.0%         3.8%         0.0%      |  40.9%        40.1%        52.5%        37.4%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  2/14 (14%)   0/15 (0%)    0/15 (0%)    0/12 (0%)  |  6/21 (29%)   7/26 (27%)   8/20 (40%)   8/26 (31%) |
|FIRST INCIDENCE (DAYS) |   733 (T)      ---          681          ---       |   468          475          614          467       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.224N     P=0.221N     P=0.484N     P=0.270N   |  P=0.414N     P=0.574N     P=0.297      P=0.439N   |
|INCIDENTAL TUMOR       |  P=0.207N     P=0.221N     P=0.484N     P=0.270N   |  P=0.487N     P=0.587      P=0.350      P=0.449N   |
|LOGISTIC REGRESSION    |  P=0.215N     P=0.221N     P=0.499N     P=0.270N   |  P=0.518N     P=0.466      P=0.301      P=0.581N   |
|COCHRAN-ARMITAGE       |  P=0.196N                                          |  P=0.505N                                          |
|FISHER EXACT           |               P=0.248N     P=0.500N     P=0.252N   |               P=0.413      P=0.333      P=0.589N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma or Adenoma                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/65 (3%)    0/65 (0%)    1/65 (2%)    0/64 (0%)  | 13/65 (20%)  15/65 (23%)  16/65 (25%)  13/65 (20%) |
|ADJUSTED (b)           |  14.3%         0.0%         3.8%         0.0%      |  44.8%        43.3%        53.6%        40.9%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  2/14 (14%)   0/15 (0%)    0/15 (0%)    0/12 (0%)  |  7/21 (33%)   8/26 (31%)   8/20 (40%)   9/26 (35%) |
|FIRST INCIDENCE (DAYS) |   733 (T)      ---          681          ---       |   468          475          611          467       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.224N     P=0.221N     P=0.484N     P=0.270N   |  P=0.409N     P=0.555N     P=0.301      P=0.422N   |
|INCIDENTAL TUMOR       |  P=0.207N     P=0.221N     P=0.484N     P=0.270N   |  P=0.478N     P=0.575N     P=0.342      P=0.430N   |
|LOGISTIC REGRESSION    |  P=0.215N     P=0.221N     P=0.499N     P=0.270N   |  P=0.519N     P=0.475      P=0.304      P=0.578N   |
|COCHRAN-ARMITAGE       |  P=0.196N                                          |  P=0.505N                                          |
|FISHER EXACT           |               P=0.248N     P=0.500N     P=0.252N   |               P=0.416      P=0.337      P=0.587N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE  11
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Fibroma, Fibroadenoma, Carcinoma, or Adenoma                                                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/65 (3%)    0/65 (0%)    1/65 (2%)    0/64 (0%)  | 13/65 (20%)  15/65 (23%)  17/65 (26%)  14/65 (22%) |
|ADJUSTED (b)           |  14.3%         0.0%         3.8%         0.0%      |  44.8%        43.3%        54.9%        42.1%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  2/14 (14%)   0/15 (0%)    0/15 (0%)    0/12 (0%)  |  7/21 (33%)   8/26 (31%)   8/20 (40%)   9/26 (35%) |
|FIRST INCIDENCE (DAYS) |   733 (T)      ---          681          ---       |   468          475          611          467       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.224N     P=0.221N     P=0.484N     P=0.270N   |  P=0.506N     P=0.555N     P=0.237      P=0.509N   |
|INCIDENTAL TUMOR       |  P=0.207N     P=0.221N     P=0.484N     P=0.270N   |  P=0.513      P=0.575N     P=0.260      P=0.486N   |
|LOGISTIC REGRESSION    |  P=0.215N     P=0.221N     P=0.499N     P=0.270N   |  P=0.466      P=0.475      P=0.233      P=0.512    |
|COCHRAN-ARMITAGE       |  P=0.196N                                          |  P=0.479                                           |
|FISHER EXACT           |               P=0.248N     P=0.500N     P=0.252N   |               P=0.416      P=0.266      P=0.500    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 24/58 (41%)  19/57 (33%)  16/57 (28%)  12/57 (21%) | 21/57 (37%)  24/59 (41%)  19/60 (32%)  21/60 (35%) |
|ADJUSTED (b)           |  75.2%        67.9%        55.9%        47.8%      |  58.1%        62.2%        60.3%        56.5%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/2 (0%)     0/3 (0%)     0/1 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     1/5 (20%)    0/5 (0%)     0/5 (0%)   |  1/5 (20%)    3/5 (60%)    0/5 (0%)     1/5 (20%)  |
|TERMINAL (d)           |  7/13 (54%)   8/15 (53%)   5/14 (36%)   3/12 (25%) |  7/20 (35%)  13/26 (50%)   8/19 (42%)  11/26 (42%) |
|FIRST INCIDENCE (DAYS) |   569          459 (I)      367          539       |   403          460 (I)      536          460 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.046N*    P=0.170N     P=0.121N     P=0.052N   |  P=0.329N     P=0.513N     P=0.479N     P=0.384N   |
|INCIDENTAL TUMOR       |  P=0.013N*    P=0.226N     P=0.111N     P=0.016N*  |  P=0.428N     P=0.393      P=0.419N     P=0.532N   |
|LOGISTIC REGRESSION    |  P=0.014N*    P=0.174N     P=0.094N     P=0.016N*  |  P=0.408N     P=0.425      P=0.433N     P=0.518N   |
|COCHRAN-ARMITAGE       |  P=0.011N*                                         |  P=0.365N                                          |
|FISHER EXACT           |               P=0.242N     P=0.096N     P=0.015N*  |               P=0.408      P=0.346N     P=0.494N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE  12
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma                                                                                                                   |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/58 (0%)    0/57 (0%)    0/57 (0%)    0/57 (0%)  |  1/57 (2%)    3/59 (5%)    1/60 (2%)    2/60 (3%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   2.2%         7.5%         3.8%         5.1%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/2 (0%)     0/3 (0%)     0/1 (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)           |  0/13 (0%)    0/15 (0%)    0/14 (0%)    0/12 (0%)  |  0/20 (0%)    0/26 (0%)    0/19 (0%)    0/26 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   563          509          713          550       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.527      P=0.326      P=0.747      P=0.490    |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.523      P=0.371      P=0.734      P=0.401    |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.555      P=0.325      P=0.755N     P=0.533    |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.547                                           |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.322      P=0.739N     P=0.519    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis or Unspecified Site                                                                               |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 24/58 (41%)  19/57 (33%)  16/57 (28%)  12/57 (21%) | 22/57 (39%)  27/59 (46%)  20/60 (33%)  23/60 (38%) |
|ADJUSTED (b)           |  75.2%        67.9%        55.9%        47.8%      |  59.0%        65.1%        61.8%        58.7%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/2 (0%)     0/3 (0%)     0/1 (0%)   |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     1/5 (20%)    0/5 (0%)     0/5 (0%)   |  1/5 (20%)    3/5 (60%)    0/5 (0%)     1/5 (20%)  |
|TERMINAL (d)           |  7/13 (54%)   8/15 (53%)   5/14 (36%)   3/12 (25%) |  7/20 (35%)  13/26 (50%)   8/19 (42%)  11/26 (42%) |
|FIRST INCIDENCE (DAYS) |   569          459 (I)      367          539       |   403          460 (I)      536          460 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.046N*    P=0.170N     P=0.121N     P=0.052N   |  P=0.359N     P=0.494      P=0.483N     P=0.455N   |
|INCIDENTAL TUMOR       |  P=0.013N*    P=0.226N     P=0.111N     P=0.016N*  |  P=0.460N     P=0.283      P=0.429N     P=0.513    |
|LOGISTIC REGRESSION    |  P=0.014N*    P=0.174N     P=0.094N     P=0.016N*  |  P=0.430N     P=0.284      P=0.432N     P=0.565    |
|COCHRAN-ARMITAGE       |  P=0.011N*                                         |  P=0.387N                                          |
|FISHER EXACT           |               P=0.242N     P=0.096N     P=0.015N*  |               P=0.277      P=0.344N     P=0.564N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE  13
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal Cell Adenoma                                                                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/65 (3%)    0/65 (0%)    1/65 (2%)    0/64 (0%)  |  1/65 (2%)    0/65 (0%)    0/65 (0%)    0/65 (0%)  |
|ADJUSTED (b)           |  14.3%         0.0%         4.8%         0.0%      |   4.8%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  2/14 (14%)   0/15 (0%)    0/15 (0%)    0/12 (0%)  |  1/21 (5%)    0/26 (0%)    0/20 (0%)    0/26 (0%)  |
|FIRST INCIDENCE (DAYS) |   733 (T)      ---          706          ---       |   729 (T)      ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.207N     P=0.221N     P=0.466N     P=0.270N   |  P=0.308N     P=0.457N     P=0.510N     P=0.457N   |
|INCIDENTAL TUMOR       |  P=0.207N     P=0.221N     P=0.484N     P=0.270N   |  P=0.308N     P=0.457N     P=0.510N     P=0.457N   |
|LOGISTIC REGRESSION    |  P=0.215N     P=0.221N     P=0.493N     P=0.270N   |  P=0.308N     P=0.457N     P=0.510N     P=0.457N   |
|COCHRAN-ARMITAGE       |  P=0.196N                                          |  P=0.323N                                          |
|FISHER EXACT           |               P=0.248N     P=0.500N     P=0.252N   |               P=0.500N     P=0.500N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal Cell Adenoma, Basosquamous Tumor Benign, or Trichoepithelioma                                                         |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/65 (3%)    0/65 (0%)    2/65 (3%)    0/64 (0%)  |  1/65 (2%)    0/65 (0%)    0/65 (0%)    0/65 (0%)  |
|ADJUSTED (b)           |  14.3%         0.0%        10.1%         0.0%      |   4.8%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  2/14 (14%)   0/15 (0%)    0/15 (0%)    0/12 (0%)  |  1/21 (5%)    0/26 (0%)    0/20 (0%)    0/26 (0%)  |
|FIRST INCIDENCE (DAYS) |   733 (T)      ---          706          ---       |   729 (T)      ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.266N     P=0.221N     P=0.667N     P=0.270N   |  P=0.308N     P=0.457N     P=0.510N     P=0.457N   |
|INCIDENTAL TUMOR       |  P=0.263N     P=0.221N     P=0.682N     P=0.270N   |  P=0.308N     P=0.457N     P=0.510N     P=0.457N   |
|LOGISTIC REGRESSION    |  P=0.280N     P=0.221N     P=0.695N     P=0.270N   |  P=0.308N     P=0.457N     P=0.510N     P=0.457N   |
|COCHRAN-ARMITAGE       |  P=0.251N                                          |  P=0.323N                                          |
|FISHER EXACT           |               P=0.248N     P=0.690N     P=0.252N   |               P=0.500N     P=0.500N     P=0.500N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE  14
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal Cell Carcinoma, Basal Cell Adenoma, Basosquamous Tumor (benign,                                                       |
|     malignant or NOS), or Trichoepithelioma                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/65 (3%)    0/65 (0%)    2/65 (3%)    0/64 (0%)  |  1/65 (2%)    0/65 (0%)    0/65 (0%)    0/65 (0%)  |
|ADJUSTED (b)           |  14.3%         0.0%        10.1%         0.0%      |   4.8%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  2/14 (14%)   0/15 (0%)    0/15 (0%)    0/12 (0%)  |  1/21 (5%)    0/26 (0%)    0/20 (0%)    0/26 (0%)  |
|FIRST INCIDENCE (DAYS) |   733 (T)      ---          706          ---       |   729 (T)      ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.266N     P=0.221N     P=0.667N     P=0.270N   |  P=0.308N     P=0.457N     P=0.510N     P=0.457N   |
|INCIDENTAL TUMOR       |  P=0.263N     P=0.221N     P=0.682N     P=0.270N   |  P=0.308N     P=0.457N     P=0.510N     P=0.457N   |
|LOGISTIC REGRESSION    |  P=0.280N     P=0.221N     P=0.695N     P=0.270N   |  P=0.308N     P=0.457N     P=0.510N     P=0.457N   |
|COCHRAN-ARMITAGE       |  P=0.251N                                          |  P=0.323N                                          |
|FISHER EXACT           |               P=0.248N     P=0.690N     P=0.252N   |               P=0.500N     P=0.500N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Basal or Sq. Cell Carcinoma, Carcinoma, Basosq. Tumor (M or B), Basal                                                       |
|     Cell Adenoma, Adenoma, Papilloma, Sq Papilloma, Keratoacanthoma, Trichoepithelioma                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/65 (5%)    2/65 (3%)    4/65 (6%)    2/64 (3%)  |  4/65 (6%)    0/65 (0%)    0/65 (0%)    2/65 (3%)  |
|ADJUSTED (b)           |  16.1%         6.7%        19.5%        16.7%      |  16.2%         0.0%         0.0%         7.2%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  2/14 (14%)   0/15 (0%)    1/15 (7%)    2/12 (17%) |  3/21 (14%)   0/26 (0%)    0/20 (0%)    1/26 (4%)  |
|FIRST INCIDENCE (DAYS) |   569          570          690          733 (T)   |   564          ---          ---          718       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.544N     P=0.489N     P=0.518      P=0.566N   |  P=0.324N     P=0.045N*    P=0.069N     P=0.261N   |
|INCIDENTAL TUMOR       |  P=0.521N     P=0.554N     P=0.498      P=0.574N   |  P=0.352N     P=0.064N     P=0.076N     P=0.318N   |
|LOGISTIC REGRESSION    |  P=0.535N     P=0.493N     P=0.491      P=0.553N   |  P=0.364N     P=0.056N     P=0.065N     P=0.329N   |
|COCHRAN-ARMITAGE       |  P=0.485N                                          |  P=0.361N                                          |
|FISHER EXACT           |               P=0.500N     P=0.500      P=0.507N   |               P=0.060N     P=0.060N     P=0.340N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE  15
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibroma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/65 (5%)    1/65 (2%)    2/65 (3%)    0/64 (0%)  |  0/65 (0%)    0/65 (0%)    1/65 (2%)    2/65 (3%)  |
|ADJUSTED (b)           |   9.3%         2.4%         4.1%         0.0%      |   0.0%         0.0%         2.4%         6.9%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  0/14 (0%)    0/15 (0%)    0/15 (0%)    0/12 (0%)  |  0/21 (0%)    0/26 (0%)    0/20 (0%)    1/26 (4%)  |
|FIRST INCIDENCE (DAYS) |   566          572          525          ---       |   ---          ---          611          671       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.124N     P=0.310N     P=0.519N     P=0.150N   |  P=0.073        (e)        P=0.505      P=0.263    |
|INCIDENTAL TUMOR       |  P=0.094N     P=0.415N     P=0.469N     P=0.139N   |  P=0.067        (e)        P=0.452      P=0.221    |
|LOGISTIC REGRESSION    |  P=0.108N     P=0.305N     P=0.501N     P=0.128N   |  P=0.072        (e)        P=0.500      P=0.241    |
|COCHRAN-ARMITAGE       |  P=0.108N                                          |  P=0.072                                           |
|FISHER EXACT           |               P=0.310N     P=0.500N     P=0.125N   |                 (e)        P=0.500      P=0.248    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Fibroma, Fibrosarcoma, Sarcoma, Myxoma, Myxosarcoma, or Fibrous Histiocytoma                                                |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  3/65 (5%)    1/65 (2%)    3/65 (5%)    0/64 (0%)  |  0/65 (0%)    0/65 (0%)    2/65 (3%)    2/65 (3%)  |
|ADJUSTED (b)           |   9.3%         2.4%        10.5%         0.0%      |   0.0%         0.0%         4.8%         6.9%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  0/14 (0%)    0/15 (0%)    1/15 (7%)    0/12 (0%)  |  0/21 (0%)    0/26 (0%)    0/20 (0%)    1/26 (4%)  |
|FIRST INCIDENCE (DAYS) |   566          572          525          ---       |   ---          ---          611          671       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.159N     P=0.310N     P=0.648      P=0.150N   |  P=0.089        (e)        P=0.242      P=0.263    |
|INCIDENTAL TUMOR       |  P=0.124N     P=0.415N     P=0.632N     P=0.139N   |  P=0.086        (e)        P=0.183      P=0.221    |
|LOGISTIC REGRESSION    |  P=0.139N     P=0.305N     P=0.658      P=0.128N   |  P=0.090        (e)        P=0.238      P=0.241    |
|COCHRAN-ARMITAGE       |  P=0.137N                                          |  P=0.091                                           |
|FISHER EXACT           |               P=0.310N     P=0.660N     P=0.125N   |                 (e)        P=0.248      P=0.248    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE  16
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/65 (0%)    1/65 (2%)    1/65 (2%)    0/64 (0%)  |  2/65 (3%)    0/65 (0%)    0/65 (0%)    0/65 (0%)  |
|ADJUSTED (b)           |   0.0%         2.3%         4.2%         0.0%      |   6.9%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  0/14 (0%)    0/15 (0%)    0/15 (0%)    0/12 (0%)  |  1/21 (5%)    0/26 (0%)    0/20 (0%)    0/26 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          570          690          ---       |   564          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.628N     P=0.491      P=0.492        (e)      |  P=0.122N     P=0.216N     P=0.248N     P=0.219N   |
|INCIDENTAL TUMOR       |  P=0.596N     P=0.408      P=0.500        (e)      |  P=0.130N     P=0.301N     P=0.272N     P=0.241N   |
|LOGISTIC REGRESSION    |  P=0.600N     P=0.500      P=0.496        (e)      |  P=0.125N     P=0.233N     P=0.240N     P=0.236N   |
|COCHRAN-ARMITAGE       |  P=0.594N                                          |  P=0.125N                                          |
|FISHER EXACT           |               P=0.500      P=0.500        (e)      |               P=0.248N     P=0.248N     P=0.248N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma or Papilloma                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/65 (0%)    1/65 (2%)    1/65 (2%)    1/64 (2%)  |  2/65 (3%)    0/65 (0%)    0/65 (0%)    1/65 (2%)  |
|ADJUSTED (b)           |   0.0%         2.3%         4.2%         8.3%      |   6.9%         0.0%         0.0%         3.8%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  0/14 (0%)    0/15 (0%)    0/15 (0%)    1/12 (8%)  |  1/21 (5%)    0/26 (0%)    0/20 (0%)    1/26 (4%)  |
|FIRST INCIDENCE (DAYS) |   ---          570          690          733 (T)   |   564          ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.350      P=0.491      P=0.492      P=0.469    |  P=0.459N     P=0.216N     P=0.248N     P=0.453N   |
|INCIDENTAL TUMOR       |  P=0.376      P=0.408      P=0.500      P=0.469    |  P=0.463N     P=0.301N     P=0.272N     P=0.478N   |
|LOGISTIC REGRESSION    |  P=0.375      P=0.500      P=0.496      P=0.469    |  P=0.483N     P=0.233N     P=0.240N     P=0.496N   |
|COCHRAN-ARMITAGE       |  P=0.391                                           |  P=0.481N                                          |
|FISHER EXACT           |               P=0.500      P=0.500      P=0.496    |               P=0.248N     P=0.248N     P=0.500N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE  17
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma, Papilloma, Squamous Cell Carcinoma or Keratoacanthoma                                              |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/65 (2%)    2/65 (3%)    2/65 (3%)    2/64 (3%)  |  3/65 (5%)    0/65 (0%)    0/65 (0%)    2/65 (3%)  |
|ADJUSTED (b)           |   2.1%         6.7%        10.6%        16.7%      |  11.5%         0.0%         0.0%         7.2%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  0/14 (0%)    0/15 (0%)    1/15 (7%)    2/12 (17%) |  2/21 (10%)   0/26 (0%)    0/20 (0%)    1/26 (4%)  |
|FIRST INCIDENCE (DAYS) |   569          570          690          733 (T)   |   564          ---          ---          718       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.369      P=0.498      P=0.493      P=0.454    |  P=0.517N     P=0.098N     P=0.129N     P=0.424N   |
|INCIDENTAL TUMOR       |  P=0.394      P=0.414      P=0.481      P=0.444    |  P=0.551N     P=0.138N     P=0.143N     P=0.497N   |
|LOGISTIC REGRESSION    |  P=0.394      P=0.501      P=0.493      P=0.471    |  P=0.557N     P=0.113N     P=0.123N     P=0.494N   |
|COCHRAN-ARMITAGE       |  P=0.424                                           |  P=0.553N                                          |
|FISHER EXACT           |               P=0.500      P=0.500      P=0.494    |               P=0.122N     P=0.122N     P=0.500N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Squamous Cell Papilloma, Papilloma, or Keratoacanthoma                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/65 (2%)    1/65 (2%)    2/65 (3%)    2/64 (3%)  |  3/65 (5%)    0/65 (0%)    0/65 (0%)    1/65 (2%)  |
|ADJUSTED (b)           |   2.1%         2.3%        10.6%        16.7%      |  11.5%         0.0%         0.0%         3.8%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  0/14 (0%)    0/15 (0%)    1/15 (7%)    2/12 (17%) |  2/21 (10%)   0/26 (0%)    0/20 (0%)    1/26 (4%)  |
|FIRST INCIDENCE (DAYS) |   569          570          690          733 (T)   |   564          ---          ---          729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.289      P=0.748      P=0.493      P=0.454    |  P=0.244N     P=0.098N     P=0.129N     P=0.252N   |
|INCIDENTAL TUMOR       |  P=0.307      P=0.657      P=0.481      P=0.444    |  P=0.249N     P=0.138N     P=0.143N     P=0.270N   |
|LOGISTIC REGRESSION    |  P=0.314      P=0.762      P=0.493      P=0.471    |  P=0.267N     P=0.113N     P=0.123N     P=0.300N   |
|COCHRAN-ARMITAGE       |  P=0.338                                           |  P=0.266N                                          |
|FISHER EXACT           |               P=0.752N     P=0.500      P=0.494    |               P=0.122N     P=0.122N     P=0.310N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE  18
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 43/59 (73%)  50/58 (86%)  43/58 (74%)  51/57 (89%) |                                                    |
|ADJUSTED (b)           |  95.1%       100.0%       100.0%       100.0%      |                                                    |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |                                                    |
|INTERIM SACRIFICE 2 (c)|  3/5 (60%)    4/5 (80%)    0/5 (0%)     4/5 (80%)  |                                                    |
|TERMINAL (d)           | 12/14 (86%)  15/15 (100%) 15/15 (100%) 12/12 (100%)|                                                    |
|FIRST INCIDENCE (DAYS) |   459 (I)      459 (I)      457          459 (I)   |                                                    |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.060      P=0.328      P=0.544N     P=0.064    |                                                    |
|INCIDENTAL TUMOR       |  P=0.039 *    P=0.090      P=0.510      P=0.025 *  |                                                    |
|LOGISTIC REGRESSION    |  P=0.027 *    P=0.069      P=0.471      P=0.017 *  |                                                    |
|COCHRAN-ARMITAGE       |  P=0.045 *                                         |                                                    |
|FISHER EXACT           |               P=0.059      P=0.522      P=0.020 *  |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  7/59 (12%)   5/58 (9%)    5/57 (9%)    2/57 (4%)  |  2/57 (4%)    2/57 (4%)    3/58 (5%)    2/58 (3%)  |
|ADJUSTED (b)           |  29.3%        18.1%        26.1%        13.2%      |   6.5%         4.2%        15.0%         7.7%      |
|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%)     1/5 (20%)    0/5 (0%)   |  1/5 (20%)    1/5 (20%)    0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  2/14 (14%)   0/15 (0%)    3/15 (20%)   1/12 (8%)  |  1/21 (5%)    0/26 (0%)    3/20 (15%)   2/26 (8%)  |
|FIRST INCIDENCE (DAYS) |   459 (I)      647          459 (I)      697       |   460 (I)      460 (I)      729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.105N     P=0.341N     P=0.352N     P=0.126N   |  P=0.573N     P=0.670N     P=0.482      P=0.636N   |
|INCIDENTAL TUMOR       |  P=0.069N     P=0.262N     P=0.347N     P=0.074N   |  P=0.571N     P=0.645      P=0.482      P=0.636N   |
|LOGISTIC REGRESSION    |  P=0.082N     P=0.377N     P=0.405N     P=0.095N   |  P=0.583      P=0.670      P=0.497      P=0.689N   |
|COCHRAN-ARMITAGE       |  P=0.075N                                          |  P=0.585                                           |
|FISHER EXACT           |               P=0.393N     P=0.406N     P=0.090N   |               P=0.691N     P=0.508      P=0.684N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE  19
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  8/59 (14%)   5/58 (9%)    6/57 (11%)   2/57 (4%)  |  2/57 (4%)    2/57 (4%)    3/58 (5%)    2/58 (3%)  |
|ADJUSTED (b)           |  33.8%        18.1%        28.0%        13.2%      |   6.5%         4.2%        15.0%         7.7%      |
|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%)     1/5 (20%)    0/5 (0%)   |  1/5 (20%)    1/5 (20%)    0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  2/14 (14%)   0/15 (0%)    3/15 (20%)   1/12 (8%)  |  1/21 (5%)    0/26 (0%)    3/20 (15%)   2/26 (8%)  |
|FIRST INCIDENCE (DAYS) |   459 (I)      647          459 (I)      697       |   460 (I)      460 (I)      729 (T)      729 (T)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.079N     P=0.245N     P=0.360N     P=0.081N   |  P=0.573N     P=0.670N     P=0.482      P=0.636N   |
|INCIDENTAL TUMOR       |  P=0.050N     P=0.170N     P=0.370N     P=0.042N*  |  P=0.571N     P=0.645      P=0.482      P=0.636N   |
|LOGISTIC REGRESSION    |  P=0.060N     P=0.272N     P=0.415N     P=0.059N   |  P=0.583      P=0.670      P=0.497      P=0.689N   |
|COCHRAN-ARMITAGE       |  P=0.054N                                          |  P=0.585                                           |
|FISHER EXACT           |               P=0.290N     P=0.415N     P=0.053N   |               P=0.691N     P=0.508      P=0.684N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Adenoma                                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  1/59 (2%)    3/58 (5%)    2/57 (4%)    1/57 (2%)  |  0/57 (0%)    0/57 (0%)    0/58 (0%)    0/58 (0%)  |
|ADJUSTED (b)           |   4.5%         9.8%        13.3%         3.7%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/14 (0%)    0/15 (0%)    2/15 (13%)   0/12 (0%)  |  0/21 (0%)    0/26 (0%)    0/20 (0%)    0/26 (0%)  |
|FIRST INCIDENCE (DAYS) |   699          629          733 (T)      660       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.529N     P=0.349      P=0.511      P=0.730    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.494N     P=0.309      P=0.516      P=0.750N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.512N     P=0.310      P=0.505      P=0.745    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.484N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.303      P=0.487      P=0.743    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE  20
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Carcinoma or Adenoma                                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |                                                    |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  2/59 (3%)    3/58 (5%)    2/57 (4%)    2/57 (4%)  |  0/57 (0%)    0/57 (0%)    0/58 (0%)    0/58 (0%)  |
|ADJUSTED (b)           |   9.8%         9.8%        13.3%         7.0%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/0          0/0          0/0          0/0        |  0/0          0/0          0/0          0/0        |
|INTERIM SACRIFICE 2 (c)|  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |  0/5 (0%)     0/5 (0%)     0/5 (0%)     0/5 (0%)   |
|TERMINAL (d)           |  0/14 (0%)    0/15 (0%)    2/15 (13%)   0/12 (0%)  |  0/21 (0%)    0/26 (0%)    0/20 (0%)    0/26 (0%)  |
|FIRST INCIDENCE (DAYS) |   699          629          733 (T)      647       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.590N     P=0.541      P=0.690N     P=0.648    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.546N     P=0.522      P=0.682N     P=0.678N   |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.572N     P=0.510      P=0.696N     P=0.666    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.541N                                          |    (e)                                             |
|FISHER EXACT           |               P=0.492      P=0.678      P=0.678    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|Tissue NOS                                                                                                                       |
|     Lipoma                                                                                                                      |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/65 (0%)    0/65 (0%)    2/65 (3%)    0/64 (0%)  |  0/65 (0%)    0/65 (0%)    2/65 (3%)    0/65 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         9.1%         0.0%      |   0.0%         0.0%         6.9%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  0/14 (0%)    0/15 (0%)    1/15 (7%)    0/12 (0%)  |  0/21 (0%)    0/26 (0%)    1/20 (5%)    0/26 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          618          ---       |   ---          ---          466          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.591        (e)        P=0.244        (e)      |  P=0.638        (e)        P=0.237        (e)      |
|INCIDENTAL TUMOR       |  P=0.596        (e)        P=0.221        (e)      |  P=0.682        (e)        P=0.335        (e)      |
|LOGISTIC REGRESSION    |  P=0.604        (e)        P=0.233        (e)      |  P=0.621        (e)        P=0.238        (e)      |
|COCHRAN-ARMITAGE       |  P=0.618                                           |  P=0.620                                           |
|FISHER EXACT           |                 (e)        P=0.248        (e)      |                 (e)        P=0.248        (e)      |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE  21
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|Tissue NOS                                                                                                                       |
|     Squamous Cell Carcinoma                                                                                                     |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/65 (0%)    0/65 (0%)    0/65 (0%)    0/64 (0%)  |  3/65 (5%)    0/65 (0%)    0/65 (0%)    0/65 (0%)  |
|ADJUSTED (b)           |   0.0%         0.0%         0.0%         0.0%      |   9.6%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  0/14 (0%)    0/15 (0%)    0/15 (0%)    0/12 (0%)  |  0/21 (0%)    0/26 (0%)    0/20 (0%)    0/26 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          ---          ---          ---       |   586          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |    (e)          (e)          (e)          (e)      |  P=0.055N     P=0.110N     P=0.134N     P=0.119N   |
|INCIDENTAL TUMOR       |    (e)          (e)          (e)          (e)      |  P=0.068N     P=0.168N     P=0.135N     P=0.184N   |
|LOGISTIC REGRESSION    |    (e)          (e)          (e)          (e)      |  P=0.053N     P=0.114N     P=0.123N     P=0.119N   |
|COCHRAN-ARMITAGE       |    (e)                                             |  P=0.053N                                          |
|FISHER EXACT           |                 (e)          (e)          (e)      |               P=0.122N     P=0.122N     P=0.122N   |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Polyp Stromal                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |                                                    |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |                                                    |  9/65 (14%)   2/65 (3%)    8/65 (12%)   6/65 (9%)  |
|ADJUSTED (b)           |                                                    |  34.3%         7.3%        24.4%        18.4%      |
|INTERIM SACRIFICE 1 (c)|                                                    |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (0%)   |
|INTERIM SACRIFICE 2 (c)|                                                    |  0/5 (0%)     0/5 (0%)     2/5 (40%)    1/5 (20%)  |
|TERMINAL (d)           |                                                    |  6/21 (29%)   1/26 (4%)    1/20 (5%)    4/26 (15%) |
|FIRST INCIDENCE (DAYS) |                                                    |   618          725          460 (I)      460 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |                                                    |  P=0.407N     P=0.014N*    P=0.526N     P=0.200N   |
|INCIDENTAL TUMOR       |                                                    |  P=0.464N     P=0.027N*    P=0.555N     P=0.196N   |
|LOGISTIC REGRESSION    |                                                    |  P=0.465N     P=0.019N*    P=0.513N     P=0.281N   |
|COCHRAN-ARMITAGE       |                                                    |  P=0.462N                                          |
|FISHER EXACT           |                                                    |               P=0.027N*    P=0.500N     P=0.292N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE  22
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Hemangiosarcoma or Hemangioma                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/65 (0%)    2/65 (3%)    0/65 (0%)    0/64 (0%)  |  0/65 (0%)    2/65 (3%)    0/65 (0%)    0/65 (0%)  |
|ADJUSTED (b)           |   0.0%        11.6%         0.0%         0.0%      |   0.0%         5.8%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  0/14 (0%)    1/15 (7%)    0/15 (0%)    0/12 (0%)  |  0/21 (0%)    0/26 (0%)    0/20 (0%)    0/26 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          712          ---          ---       |   ---          660          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.446N     P=0.253        (e)          (e)      |  P=0.402N     P=0.289        (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.425N     P=0.266        (e)          (e)      |  P=0.479N     P=0.235        (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.442N     P=0.253        (e)          (e)      |  P=0.411N     P=0.250        (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.412N                                          |  P=0.409N                                          |
|FISHER EXACT           |               P=0.248        (e)          (e)      |               P=0.248        (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated                                                          |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 31/65 (48%)  32/65 (49%)  26/65 (40%)  35/64 (55%) | 22/65 (34%)  19/65 (29%)  21/65 (32%)  18/65 (28%) |
|ADJUSTED (b)           |  77.2%        73.3%        63.0%        90.1%      |  57.1%        47.6%        55.6%        44.7%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  7/14 (50%)   5/15 (33%)   3/15 (20%)   9/12 (75%) |  7/21 (33%)   8/26 (31%)   6/20 (30%)   6/26 (23%) |
|FIRST INCIDENCE (DAYS) |   475          503          202          536       |   348          423          494          466       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.155      P=0.521N     P=0.309N     P=0.173    |  P=0.269N     P=0.222N     P=0.544N     P=0.221N   |
|INCIDENTAL TUMOR       |  P=0.204      P=0.409      P=0.288N     P=0.187    |  P=0.323N     P=0.470N     P=0.558N     P=0.361N   |
|LOGISTIC REGRESSION    |  P=0.232      P=0.401      P=0.278N     P=0.201    |  P=0.259N     P=0.304N     P=0.517N     P=0.268N   |
|COCHRAN-ARMITAGE       |  P=0.266                                           |  P=0.293N                                          |
|FISHER EXACT           |               P=0.500      P=0.240N     P=0.268    |               P=0.353N     P=0.500N     P=0.284N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE  23
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Mesothelioma: Benign, Malignant, NOS                                                                                        |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            |  0/65 (0%)    1/65 (2%)    0/65 (0%)    2/64 (3%)  |  0/65 (0%)    0/65 (0%)    0/65 (0%)    0/65 (0%)  |
|ADJUSTED (b)           |   0.0%         2.0%         0.0%        10.1%      |   0.0%         0.0%         0.0%         0.0%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  0/14 (0%)    0/15 (0%)    0/15 (0%)    1/12 (8%)  |  0/21 (0%)    0/26 (0%)    0/20 (0%)    0/26 (0%)  |
|FIRST INCIDENCE (DAYS) |   ---          524          ---          467       |   ---          ---          ---          ---       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.129      P=0.496        (e)        P=0.221    |    (e)          (e)          (e)          (e)      |
|INCIDENTAL TUMOR       |  P=0.162      P=0.612        (e)        P=0.281    |    (e)          (e)          (e)          (e)      |
|LOGISTIC REGRESSION    |  P=0.138      P=0.499        (e)        P=0.233    |    (e)          (e)          (e)          (e)      |
|COCHRAN-ARMITAGE       |  P=0.137                                           |    (e)                                             |
|FISHER EXACT           |               P=0.500        (e)        P=0.244    |                 (e)          (e)          (e)      |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Benign Tumors                                                                                                               |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 56/65 (86%)  55/65 (85%)  55/65 (85%)  57/64 (89%) | 40/65 (62%)  42/65 (65%)  40/65 (62%)  44/65 (68%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  90.5%        87.0%        92.6%        95.4%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     1/7 (14%)    0/6 (0%)   |
|INTERIM SACRIFICE 2 (c)|  4/5 (80%)    4/5 (80%)    3/5 (60%)    5/5 (100%) |  1/5 (20%)    4/5 (80%)    2/5 (40%)    3/5 (60%)  |
|TERMINAL (d)           | 14/14 (100%) 15/15 (100%) 15/15 (100%) 12/12 (100%)| 17/21 (81%)  20/26 (77%)  17/20 (85%)  24/26 (92%) |
|FIRST INCIDENCE (DAYS) |   459 (I)      459 (I)      367          459 (I)   |   403          460 (I)      200 (I)      460 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.170      P=0.380N     P=0.506N     P=0.244    |  P=0.480      P=0.334N     P=0.474      P=0.512N   |
|INCIDENTAL TUMOR       |  P=0.121      P=0.467N     P=0.686N     P=0.259    |  P=0.282      P=0.540      P=0.555      P=0.435    |
|LOGISTIC REGRESSION    |  P=0.094      P=0.521N     P=0.581      P=0.214    |  P=0.247      P=0.523      P=0.554      P=0.285    |
|COCHRAN-ARMITAGE       |  P=0.324                                           |  P=0.284                                           |
|FISHER EXACT           |               P=0.500N     P=0.500N     P=0.408    |               P=0.428      P=0.571N     P=0.291    |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE  24
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 TERMINAL SACRIFICE AT 105 WEEKS
|=================================================================================================================================|
|                       |                                                    |                                                    |
|                       |                       MALES                        |                      FEMALES                       |
|                       |                                                    |                                                    |
|DOSE                   |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |   0 MG/M3      0.62MGM3     1.25MGM3     2.5MG/M3  |
|                       |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |   LUNGTX       LUNGTX       LUNGTX       LUNGTX    |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant Tumors                                                                                                            |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 37/65 (57%)  38/65 (58%)  35/65 (54%)  43/64 (67%) | 32/65 (49%)  26/65 (40%)  30/65 (46%)  25/65 (38%) |
|ADJUSTED (b)           |  84.1%        80.1%        77.8%        97.3%      |  69.2%        57.8%        72.1%        55.0%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     0/7 (0%)     0/6 (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)           |  8/14 (57%)   6/15 (40%)   6/15 (40%)  11/12 (92%) |  8/21 (38%)   9/26 (35%)  10/20 (50%)   7/26 (27%) |
|FIRST INCIDENCE (DAYS) |   475          466          202          467       |   348          423          436          466       |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.089      P=0.504N     P=0.465N     P=0.116    |  P=0.193N     P=0.121N     P=0.502N     P=0.136N   |
|INCIDENTAL TUMOR       |  P=0.078      P=0.476      P=0.522N     P=0.099    |  P=0.193N     P=0.409N     P=0.509N     P=0.251N   |
|LOGISTIC REGRESSION    |  P=0.090      P=0.417      P=0.483N     P=0.089    |  P=0.123N     P=0.162N     P=0.403N     P=0.095N   |
|COCHRAN-ARMITAGE       |  P=0.136                                           |  P=0.182N                                          |
|FISHER EXACT           |               P=0.500      P=0.430N     P=0.154    |               P=0.189N     P=0.430N     P=0.144N   |
|=================================================================================================================================|
|                                                                                                                                 |
|All Organs                                                                                                                       |
|     Malignant and Benign Tumors                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES            |    #            #            #            #        |    #            #            #            #        |
|-----------            |                                                    |                                                    |
|OVERALL (a)            | 57/65 (88%)  57/65 (88%)  56/65 (86%)  57/64 (89%) | 53/65 (82%)  53/65 (82%)  54/65 (83%)  53/65 (82%) |
|ADJUSTED (b)           | 100.0%       100.0%       100.0%       100.0%      |  98.1%        94.6%       100.0%        96.4%      |
|INTERIM SACRIFICE 1 (c)|  0/6 (0%)     0/7 (0%)     0/7 (0%)     0/7 (0%)   |  0/7 (0%)     0/7 (0%)     1/7 (14%)    0/6 (0%)   |
|INTERIM SACRIFICE 2 (c)|  4/5 (80%)    4/5 (80%)    3/5 (60%)    5/5 (100%) |  1/5 (20%)    4/5 (80%)    2/5 (40%)    3/5 (60%)  |
|TERMINAL (d)           | 14/14 (100%) 15/15 (100%) 15/15 (100%) 12/12 (100%)| 20/21 (95%)  23/26 (88%)  20/20 (100%) 24/26 (92%) |
|FIRST INCIDENCE (DAYS) |   459 (I)      459 (I)      202          459 (I)   |   348          423          200 (I)      460 (I)   |
|-----------------------|                                                    |                                                    |
|STATISTICAL TESTS (f)  |                                                    |                                                    |
|-----------------------|                                                    |                                                    |
|LIFE TABLE             |  P=0.217      P=0.430N     P=0.508N     P=0.280    |  P=0.384N     P=0.223N     P=0.414      P=0.304N   |
|INCIDENTAL TUMOR       |  P=0.244      P=0.773      P=0.708      P=0.500    |  P=0.467N     P=0.518      P=0.576      P=0.557N   |
|LOGISTIC REGRESSION    |  P=0.294      P=0.773      P=0.641      P=0.500    |  P=0.482N     P=0.488N     P=0.515      P=0.517N   |
|COCHRAN-ARMITAGE       |  P=0.461                                           |  P=0.536                                           |
|FISHER EXACT           |               P=0.605N     P=0.500N     P=0.513    |               P=0.589N     P=0.500      P=0.589N   |
|=================================================================================================================================|
         DATE: 05/20/95                     EXPERIMENT: 05123 TEST: 05                                                 PAGE  25
                              STATISTICAL ANALYSIS OF PRIMARY TUMORS IN RATS(FISCHER344) -- NICKEL OXIDE
                                                 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  459
          Female interim sacrifices(days): 200  460
 (d)  Observed incidence at terminal kill.
 (f)  Beneath the control incidence are the P-values associated with the trend 
      test.  Beneath the dosed group incidence are the P-values corresponding to 
      pairwise comparisons between the controls and that dosed group.  The life
      table analysis regards tumors in animals dying  prior to terminal kill as
      being (directly or indirectly) the cause of death.  The incidental tumor 
      test regards these lesions as non-fatal.  Logistic regression is an alternative
      method for analyzing the incidence of non-fatal tumors.  The Cochran-Armitage
      and Fisher's exact tests compare directly the overall incidence rates.  
      For all tests, a negative trend is indicated by "N".
 (e)  Value of Statistic cannot be computed. 
 (I)  Interim sacrifice
 (T)  Terminal sacrifice
  #   Tumor rates based on number of animals necropsied.
  *   To the right of any statistical result, indicates significance at (P<=0.05).
  **  To the right of any statistical result, indicates significance at (P<=0.01).
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.