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TDMS Study 88070-04 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10
LAB: Battelle Northwest                                        ISOBUTENE                                       DATE: 06/20/97

EXPERIMENT: 88070 TEST: 04                                                                                     TIME: 10:04:20
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:
CONT: N01-ES-15313                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C88070
PATHOLOGIST: MILLER, R.                                                                                        CAS: 115-11-0007
            

Mice(B6C3F1)
-----------------------------
FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.

                                                 ----------------
                                                 Adrenal Gland
                                                 Adrenal Medulla
                                                 Bone Marrow
                                                 Brain
                                                 Clitoral Gland
                                                 Clitoral/Preputial Gland
                                                 Epididymis
                                                 Heart
                                                 Islets, Pancreatic
                                                 Kidney
                                                 Liver
                                                 Lung
                                                 Nose
                                                 Ovary
                                                 Pancreas
                                                 Parathyroid Gland
                                                 Pituitary Gland
                                                 Preputial Gland
                                                 Prostate
                                                 Salivary Glands
                                                 Spleen
                                                 Testes
                                                 Thymus
                                                 Thyroid Gland
                                                 Urinary Bladder
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10   
LAB: Battelle Northwest                                        ISOBUTENE                                       DATE: 06/20/97     
EXPERIMENT: 88070 TEST: 04                                                                                     TIME: 10:04:20     
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:              
CONT: N01-ES-15313                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C88070     
PATHOLOGIST: MILLER, R.                                                                                        CAS: 115-11-0007   



SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
IN THE ANALYSIS OF               ISOBUTENE
===============================================================

Male Mice
------------
Organ                                 Morphology
-----                                 ----------
Adrenal Cortex                         Hypertrophy
Epididymis                             Granuloma Sperm
Liver                                  Degeneration Fatty
                                       Necrosis
Lymph Node: Iliac                      Infiltration Cellular Plasma Cell
Nose: Olfactory Epithelium             Degeneration Hyaline
Nose: Respiratory Epithelium           Degeneration Hyaline
===============================================================
Female Mice
------------
Organ                                  Morphology
-----                                  ----------
Liver                                  Eosinophilic Focus
Liver: Centrilobular                   Necrosis
Mesentery: Fat                         Necrosis
Nose: Olfactory Epithelium             Degeneration Hyaline
Nose: Respiratory Epithelium           Degeneration Hyaline
Ovary                                  Angiectasis
Spleen                                 Hematopoietic Cell Proliferation
Thyroid Gland: Follicular Cell         Hyperplasia
===============================================================
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 1
                     Statistical Analysis of Non-neoplastic Lesions in        Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     14/49 (29%)  10/49 (20%)  15/50 (30%)  16/49 (33%) |3/49 (6%)    4/50 (8%)    3/49 (6%)    5/50 (10%)   |
|POLY-3 ADJUSTED (b)|     33.3%        23.0%        36.5%        40.6%       |7.1%         9.2%         6.6%         10.9%        |
|TERMINAL (d)       |     9/28 (32%)   8/32 (25%)   10/27 (37%)  13/28 (46%) |3/32 (9%)    3/31 (10%)   2/39 (5%)    5/33 (15%)   |
|FIRST INCIDENCE    |     527          546          428          547         |735 (T)      639          686          735 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.166      P=0.161N     P=0.453      P=0.399     |P=0.334      P=0.487      P=0.572N     P=0.371      |
|POLY 3             |     P=0.128      P=0.205N     P=0.468      P=0.323     |P=0.352      P=0.516      P=0.630N     P=0.398      |
|POLY 1.5           |     P=0.152      P=0.217N     P=0.493      P=0.349     |P=0.344      P=0.517      P=0.642N     P=0.389      |
|POLY 6             |     P=0.113      P=0.195N     P=0.438      P=0.305     |P=0.358      P=0.509      P=0.616N     P=0.404      |
|LOGISTIC REGRESSION|     P=0.141      P=0.206N     P=0.462      P=0.332     |P=0.366      P=0.500      P=0.618N     P=0.371      |
|COCH-ARM / FISHERS |     P=0.215      P=0.241N     P=0.526      P=0.413     |P=0.326      P=0.511      P=0.661N     P=0.369      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Hypertrophy                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     32/49 (65%)  24/49 (49%)  24/50 (48%)  29/49 (59%) |3/49 (6%)    1/50 (2%)    4/49 (8%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     73.3%        53.8%        57.7%        70.4%       |7.1%         2.3%         8.8%         4.3%         |
|TERMINAL (d)       |     22/28 (79%)  19/32 (59%)  19/27 (70%)  22/28 (79%) |3/32 (9%)    0/31 (0%)    4/39 (10%)   0/33 (0%)    |
|FIRST INCIDENCE    |     387          512          389          341         |735 (T)      594          735 (T)      672          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.306      P=0.027N*    P=0.130N     P=0.385N    |P=0.529N     P=0.311N     P=0.608      P=0.471N     |
|POLY 3             |     P=0.267      P=0.038N*    P=0.083N     P=0.477N    |P=0.514N     P=0.293N     P=0.536      P=0.463N     |
|POLY 1.5           |     P=0.319      P=0.049N*    P=0.070N     P=0.432N    |P=0.526N     P=0.293N     P=0.523      P=0.472N     |
|POLY 6             |     P=0.233      P=0.031N*    P=0.110N     P=0.515N    |P=0.501N     P=0.297N     P=0.549      P=0.454N     |
|LOGISTIC REGRESSION|     P=0.262      P=0.043N*    P=0.091N     P=0.479N    |P=0.526N     P=0.296N     P=0.608      P=0.466N     |
|COCH-ARM / FISHERS |     P=0.442      P=0.076N     P=0.062N     P=0.339N    |P=0.544N     P=0.301N     P=0.500      P=0.490N     |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 2
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Vacuolization Cytoplasmic                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/49 (0%)    0/50 (0%)    0/49 (0%)   |1/49 (2%)    2/50 (4%)    1/49 (2%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |2.4%         4.6%         2.2%         4.4%         |
|TERMINAL (d)       |     0/28 (0%)    0/32 (0%)    0/27 (0%)    0/28 (0%)   |1/32 (3%)    2/31 (7%)    1/39 (3%)    1/33 (3%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |735 (T)      735 (T)      735 (T)      701          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.504      P=0.489      P=0.717N     P=0.522      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.513      P=0.507      P=0.746N     P=0.527      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.506      P=0.510      P=0.751N     P=0.521      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.519      P=0.501      P=0.740N     P=0.532      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.521      P=0.489      P=0.717N     P=0.530      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.492      P=0.508      P=0.753N     P=0.508      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/49 (0%)    1/50 (2%)    1/49 (2%)   |0/48 (0%)    3/49 (6%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         2.5%         2.6%        |0.0%         6.9%         0.0%         0.0%         |
|TERMINAL (d)       |     0/28 (0%)    0/32 (0%)    0/27 (0%)    0/28 (0%)   |0/32 (0%)    2/31 (7%)    0/39 (0%)    0/33 (0%)    |
|FIRST INCIDENCE    |     ---          ---          555          562         |---          639          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.322      (e)          P=0.486      P=0.481     |P=0.260N     P=0.120      (e)          (e)          |
|POLY 3             |     P=0.326      (e)          P=0.496      P=0.491     |P=0.255N     P=0.126      (e)          (e)          |
|POLY 1.5           |     P=0.332      (e)          P=0.499      P=0.493     |P=0.257N     P=0.126      (e)          (e)          |
|POLY 6             |     P=0.324      (e)          P=0.494      P=0.492     |P=0.257N     P=0.124      (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.450      (e)          P=0.531      P=0.553     |P=0.266N     P=0.126      (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.347      (e)          P=0.505      P=0.500     |P=0.267N     P=0.125      (e)          (e)          |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 3
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Epididymis                                                                                                                       |
|     Granuloma Sperm                                                                                                             |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    1/50 (2%)    5/50 (10%)  |                                                    |
|POLY-3 ADJUSTED (b)|     0.0%         2.3%         2.5%         12.5%       |                                                    |
|TERMINAL (d)       |     0/28 (0%)    0/32 (0%)    1/27 (4%)    3/28 (11%)  |                                                    |
|FIRST INCIDENCE    |     ---          562          733 (T)      631         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.005 **   P=0.509      P=0.493      P=0.035 *   |                                                    |
|POLY 3             |     P=0.004 **   P=0.513      P=0.491      P=0.027 *   |                                                    |
|POLY 1.5           |     P=0.004 **   P=0.508      P=0.495      P=0.028 *   |                                                    |
|POLY 6             |     P=0.004 **   P=0.518      P=0.488      P=0.028 *   |                                                    |
|LOGISTIC REGRESSION|     P=0.005 **   P=0.429      P=0.493      P=0.029 *   |                                                    |
|COCH-ARM / FISHERS |     P=0.005 **   P=0.500      P=0.500      P=0.028 *   |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart                                                                                                                            |
|     Cardiomyopathy                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     21/50 (42%)  18/50 (36%)  16/50 (32%)  19/50 (38%) |10/50 (20%)  10/50 (20%)  12/50 (24%)  8/50 (16%)   |
|POLY-3 ADJUSTED (b)|     48.4%        40.7%        38.4%        44.2%       |23.2%        22.4%        25.8%        17.3%        |
|TERMINAL (d)       |     14/28 (50%)  13/32 (41%)  10/27 (37%)  12/28 (43%) |7/32 (22%)   6/31 (19%)   10/39 (26%)  5/33 (15%)   |
|FIRST INCIDENCE    |     399          639          428          330         |639          567          509          653          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.477      P=0.201N     P=0.266N     P=0.447N    |P=0.279N     P=0.577      P=0.583      P=0.359N     |
|POLY 3             |     P=0.556N     P=0.300N     P=0.232N     P=0.426N    |P=0.259N     P=0.566N     P=0.482      P=0.336N     |
|POLY 1.5           |     P=0.553      P=0.315N     P=0.220N     P=0.436N    |P=0.274N     P=0.568N     P=0.460      P=0.351N     |
|POLY 6             |     P=0.533N     P=0.285N     P=0.248N     P=0.401N    |P=0.249N     P=0.578N     P=0.498      P=0.330N     |
|LOGISTIC REGRESSION|     P=0.492      P=0.257N     P=0.238N     P=0.463N    |P=0.266N     P=0.580N     P=0.472      P=0.330N     |
|COCH-ARM / FISHERS |     P=0.532N     P=0.341N     P=0.204N     P=0.419N    |P=0.309N     P=0.598N     P=0.405      P=0.398N     |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 4
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    0/48 (0%)    1/50 (2%)    1/48 (2%)   |1/47 (2%)    0/49 (0%)    1/48 (2%)    3/49 (6%)    |
|POLY-3 ADJUSTED (b)|     2.4%         0.0%         2.5%         2.6%        |2.3%         0.0%         2.2%         6.6%         |
|TERMINAL (d)       |     1/28 (4%)    0/32 (0%)    1/27 (4%)    1/28 (4%)   |0/32 (0%)    0/31 (0%)    1/39 (3%)    2/33 (6%)    |
|FIRST INCIDENCE    |     733 (T)      ---          733 (T)      733 (T)     |610          ---          735 (T)      596          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.549      P=0.473N     P=0.754      P=0.762     |P=0.085      P=0.491N     P=0.731N     P=0.325      |
|POLY 3             |     P=0.530      P=0.494N     P=0.751      P=0.745     |P=0.093      P=0.500N     P=0.751N     P=0.331      |
|POLY 1.5           |     P=0.537      P=0.499N     P=0.755      P=0.746     |P=0.089      P=0.496N     P=0.753N     P=0.327      |
|POLY 6             |     P=0.524      P=0.489N     P=0.747      P=0.746     |P=0.097      P=0.505N     P=0.748N     P=0.335      |
|LOGISTIC REGRESSION|     P=0.549      (e)          P=0.754      P=0.762     |P=0.067      P=0.476N     P=0.755      P=0.262      |
|COCH-ARM / FISHERS |     P=0.557      P=0.510N     P=0.753N     P=0.742     |P=0.084      P=0.490N     P=0.747N     P=0.324      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Infarct                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    2/49 (4%)    4/50 (8%)    0/50 (0%)   |1/49 (2%)    2/50 (4%)    1/49 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     2.4%         4.7%         9.9%         0.0%        |2.3%         4.6%         2.2%         0.0%         |
|TERMINAL (d)       |     1/28 (4%)    2/32 (6%)    1/27 (4%)    0/28 (0%)   |0/32 (0%)    1/31 (3%)    1/39 (3%)    0/33 (0%)    |
|FIRST INCIDENCE    |     733 (T)      733 (T)      499          ---         |653          639          735 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.245N     P=0.547      P=0.170      P=0.500N    |P=0.225N     P=0.493      P=0.730N     P=0.481N     |
|POLY 3             |     P=0.245N     P=0.511      P=0.172      P=0.510N    |P=0.228N     P=0.509      P=0.747N     P=0.486N     |
|POLY 1.5           |     P=0.238N     P=0.504      P=0.175      P=0.507N    |P=0.230N     P=0.511      P=0.751N     P=0.488N     |
|POLY 6             |     P=0.249N     P=0.519      P=0.171      P=0.510N    |P=0.228N     P=0.501      P=0.743N     P=0.485N     |
|LOGISTIC REGRESSION|     P=0.226N     P=0.547      P=0.181      (e)         |P=0.242N     P=0.498      P=0.761      P=0.534N     |
|COCH-ARM / FISHERS |     P=0.219N     P=0.492      P=0.181      P=0.500N    |P=0.236N     P=0.508      P=0.753N     P=0.495N     |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 5
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Metaplasia Osseous                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    0/49 (0%)    0/50 (0%)    2/50 (4%)   |1/49 (2%)    1/50 (2%)    2/49 (4%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     2.4%         0.0%         0.0%         5.1%        |2.4%         2.3%         4.4%         0.0%         |
|TERMINAL (d)       |     0/28 (0%)    0/32 (0%)    0/27 (0%)    2/28 (7%)   |1/32 (3%)    1/31 (3%)    2/39 (5%)    0/33 (0%)    |
|FIRST INCIDENCE    |     653          ---          ---          733 (T)     |735 (T)      735 (T)      735 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.164      P=0.495N     P=0.528N     P=0.490     |P=0.309N     P=0.755      P=0.569      P=0.494N     |
|POLY 3             |     P=0.163      P=0.495N     P=0.510N     P=0.481     |P=0.298N     P=0.756N     P=0.524      P=0.485N     |
|POLY 1.5           |     P=0.167      P=0.498N     P=0.506N     P=0.486     |P=0.303N     P=0.753N     P=0.516      P=0.487N     |
|POLY 6             |     P=0.160      P=0.492N     P=0.515N     P=0.478     |P=0.293N     P=0.760N     P=0.532      P=0.483N     |
|LOGISTIC REGRESSION|     P=0.163      P=0.519N     P=0.496N     P=0.484     |P=0.309N     P=0.755      P=0.569      (e)          |
|COCH-ARM / FISHERS |     P=0.177      P=0.505N     P=0.500N     P=0.500     |P=0.314N     P=0.747N     P=0.500      P=0.495N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Nephropathy                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     36/50 (72%)  39/49 (80%)  38/50 (76%)  40/50 (80%) |13/49 (27%)  14/50 (28%)  18/49 (37%)  12/50 (24%)  |
|POLY-3 ADJUSTED (b)|     80.4%        86.1%        84.5%        87.6%       |29.5%        30.6%        38.9%        25.0%        |
|TERMINAL (d)       |     24/28 (86%)  31/32 (97%)  26/27 (96%)  27/28 (96%) |7/32 (22%)   7/31 (23%)   15/39 (39%)  7/33 (21%)   |
|FIRST INCIDENCE    |     560          546          428          330         |608          567          600          527          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.157      P=0.469N     P=0.305      P=0.251     |P=0.312N     P=0.476      P=0.385      P=0.440N     |
|POLY 3             |     P=0.288      P=0.312      P=0.397      P=0.237     |P=0.260N     P=0.548      P=0.237      P=0.402N     |
|POLY 1.5           |     P=0.274      P=0.295      P=0.405      P=0.221     |P=0.283N     P=0.550      P=0.226      P=0.421N     |
|POLY 6             |     P=0.318      P=0.322      P=0.378      P=0.260     |P=0.244N     P=0.535      P=0.243      P=0.393N     |
|LOGISTIC REGRESSION|     P=0.108      P=0.408      P=0.273      P=0.118     |P=0.349N     P=0.526      P=0.229      P=0.513N     |
|COCH-ARM / FISHERS |     P=0.313      P=0.259      P=0.410      P=0.241     |P=0.337N     P=0.525      P=0.193      P=0.477N     |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 6
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Papilla                                                                                                                  |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    3/49 (6%)    6/50 (12%)   5/50 (10%)  |0/49 (0%)    0/50 (0%)    0/49 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     7.0%         7.0%         14.4%        12.1%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/28 (0%)    1/32 (3%)    0/27 (0%)    0/28 (0%)   |0/32 (0%)    0/31 (0%)    0/39 (0%)    0/33 (0%)    |
|FIRST INCIDENCE    |     399          639          512          251         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.288      P=0.627N     P=0.227      P=0.343     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.289      P=0.659N     P=0.226      P=0.335     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.299      P=0.661      P=0.231      P=0.340     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.286      P=0.653N     P=0.225      P=0.336     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.455      P=0.577      P=0.281      P=0.467     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.326      P=0.651      P=0.243      P=0.357     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Pelvis                                                                                                                   |
|     Dilatation                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    2/49 (4%)    4/50 (8%)    4/50 (8%)   |0/49 (0%)    0/50 (0%)    0/49 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     7.1%         4.6%         9.8%         9.7%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/28 (0%)    0/32 (0%)    1/27 (4%)    0/28 (0%)   |0/32 (0%)    0/31 (0%)    0/39 (0%)    0/33 (0%)    |
|FIRST INCIDENCE    |     387          512          499          457         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.316      P=0.457N     P=0.474      P=0.466     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.337      P=0.489N     P=0.483      P=0.484     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.344      P=0.497N     P=0.489      P=0.485     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.338      P=0.479N     P=0.481      P=0.491     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.508      P=0.603N     P=0.545      P=0.584     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.369      P=0.510N     P=0.500      P=0.500     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 7
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Basophilic Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     7/50 (14%)   8/50 (16%)   6/50 (12%)   5/49 (10%)  |4/47 (9%)    4/50 (8%)    2/50 (4%)    5/50 (10%)   |
|POLY-3 ADJUSTED (b)|     16.3%        17.8%        14.7%        12.6%       |9.3%         9.2%         4.4%         10.9%        |
|TERMINAL (d)       |     4/28 (14%)   4/32 (13%)   4/27 (15%)   2/28 (7%)   |3/32 (9%)    3/31 (10%)   1/39 (3%)    4/33 (12%)   |
|FIRST INCIDENCE    |     387          546          387          508         |449          639          692          701          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.326N     P=0.580      P=0.523N     P=0.407N    |P=0.405      P=0.635      P=0.268N     P=0.528      |
|POLY 3             |     P=0.341N     P=0.539      P=0.539N     P=0.437N    |P=0.412      P=0.635N     P=0.307N     P=0.541      |
|POLY 1.5           |     P=0.327N     P=0.521      P=0.524N     P=0.429N    |P=0.407      P=0.624N     P=0.310N     P=0.539      |
|POLY 6             |     P=0.343N     P=0.565      P=0.552N     P=0.432N    |P=0.417      P=0.641      P=0.301N     P=0.543      |
|LOGISTIC REGRESSION|     P=0.242N     P=0.438      P=0.465N     P=0.364N    |P=0.399      P=0.595N     P=0.317N     P=0.529      |
|COCH-ARM / FISHERS |     P=0.286N     P=0.500      P=0.500N     P=0.394N    |P=0.400      P=0.607N     P=0.310N     P=0.540      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Clear Cell Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     9/50 (18%)   4/50 (8%)    6/50 (12%)   10/49 (20%) |0/47 (0%)    4/50 (8%)    3/50 (6%)    4/50 (8%)    |
|POLY-3 ADJUSTED (b)|     21.8%        9.1%         15.2%        25.5%       |0.0%         9.1%         6.6%         8.6%         |
|TERMINAL (d)       |     9/28 (32%)   3/32 (9%)    6/27 (22%)   9/28 (32%)  |0/32 (0%)    3/31 (10%)   3/39 (8%)    1/33 (3%)    |
|FIRST INCIDENCE    |     733 (T)      649          733 (T)      508         |---          594          735 (T)      596          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.132      P=0.070N     P=0.302N     P=0.498     |P=0.230      P=0.063      P=0.158      P=0.075      |
|POLY 3             |     P=0.121      P=0.091N     P=0.316N     P=0.448     |P=0.245      P=0.065      P=0.133      P=0.073      |
|POLY 1.5           |     P=0.132      P=0.100N     P=0.305N     P=0.452     |P=0.238      P=0.066      P=0.132      P=0.071      |
|POLY 6             |     P=0.116      P=0.081N     P=0.327N     P=0.456     |P=0.255      P=0.062      P=0.136      P=0.076      |
|LOGISTIC REGRESSION|     P=0.115      P=0.080N     P=0.302N     P=0.436     |P=0.224      P=0.070      P=0.158      P=0.059      |
|COCH-ARM / FISHERS |     P=0.161      P=0.117N     P=0.288N     P=0.480     |P=0.228      P=0.066      P=0.133      P=0.066      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 8
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Degeneration Fatty                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    2/50 (4%)    5/49 (10%)  |2/47 (4%)    1/50 (2%)    5/50 (10%)   1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     2.4%         2.3%         5.0%         12.2%       |4.7%         2.3%         10.6%        2.2%         |
|TERMINAL (d)       |     1/28 (4%)    1/32 (3%)    1/27 (4%)    1/28 (4%)   |1/32 (3%)    0/31 (0%)    2/39 (5%)    0/33 (0%)    |
|FIRST INCIDENCE    |     733 (T)      733 (T)      389          341         |621          639          543          596          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.024 *    P=0.732N     P=0.492      P=0.102     |P=0.390N     P=0.501N     P=0.273      P=0.481N     |
|POLY 3             |     P=0.024 *    P=0.749N     P=0.492      P=0.098     |P=0.372N     P=0.491N     P=0.259      P=0.472N     |
|POLY 1.5           |     P=0.024 *    P=0.753N     P=0.496      P=0.096     |P=0.381N     P=0.485N     P=0.251      P=0.474N     |
|POLY 6             |     P=0.025 *    P=0.745N     P=0.488      P=0.103     |P=0.361N     P=0.500N     P=0.271      P=0.470N     |
|LOGISTIC REGRESSION|     P=0.052      P=0.732N     P=0.523      P=0.134     |P=0.479N     P=0.457N     P=0.223      P=0.536N     |
|COCH-ARM / FISHERS |     P=0.026 *    P=0.753N     P=0.500      P=0.098     |P=0.395N     P=0.477N     P=0.244      P=0.477N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Eosinophilic Focus                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     5/50 (10%)   4/50 (8%)    11/50 (22%)  7/49 (14%)  |17/47 (36%)  11/50 (22%)  12/50 (24%)  7/50 (14%)   |
|POLY-3 ADJUSTED (b)|     12.0%        9.2%         27.6%        18.2%       |39.5%        25.1%        25.6%        15.2%        |
|TERMINAL (d)       |     4/28 (14%)   3/32 (9%)    10/27 (37%)  7/28 (25%)  |13/32 (41%)  8/31 (26%)   8/39 (21%)   6/33 (18%)   |
|FIRST INCIDENCE    |     611          715          583          733 (T)     |653          639          477          596          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.294      P=0.422N     P=0.068      P=0.374     |P=0.029N*    P=0.161N     P=0.087N     P=0.014N*    |
|POLY 3             |     P=0.248      P=0.473N     P=0.065      P=0.322     |P=0.019N*    P=0.110N     P=0.116N     P=0.007N**   |
|POLY 1.5           |     P=0.270      P=0.482N     P=0.073      P=0.334     |P=0.022N*    P=0.101N     P=0.125N     P=0.008N**   |
|POLY 6             |     P=0.234      P=0.463N     P=0.058      P=0.316     |P=0.017N*    P=0.126N     P=0.106N     P=0.007N**   |
|LOGISTIC REGRESSION|     P=0.265      P=0.455N     P=0.062      P=0.333     |P=0.022N*    P=0.123N     P=0.131N     P=0.009N**   |
|COCH-ARM / FISHERS |     P=0.327      P=0.500N     P=0.086      P=0.365     |P=0.027N*    P=0.094N     P=0.139N     P=0.010N*    |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 9
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Mixed Cell Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    1/50 (2%)    0/49 (0%)   |0/47 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     0.0%         4.6%         2.5%         0.0%        |0.0%         0.0%         0.0%         2.2%         |
|TERMINAL (d)       |     0/28 (0%)    2/32 (6%)    1/27 (4%)    0/28 (0%)   |0/32 (0%)    0/31 (0%)    0/39 (0%)    1/33 (3%)    |
|FIRST INCIDENCE    |     ---          733 (T)      733 (T)      ---         |---          ---          ---          735 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.380N     P=0.268      P=0.493      (e)         |P=0.227      (e)          (e)          P=0.506      |
|POLY 3             |     P=0.381N     P=0.249      P=0.491      (e)         |P=0.238      (e)          (e)          P=0.516      |
|POLY 1.5           |     P=0.379N     P=0.244      P=0.495      (e)         |P=0.236      (e)          (e)          P=0.515      |
|POLY 6             |     P=0.379N     P=0.253      P=0.488      (e)         |P=0.241      (e)          (e)          P=0.517      |
|LOGISTIC REGRESSION|     (e)          P=0.268      P=0.493      (e)         |(e)          (e)          (e)          P=0.506      |
|COCH-ARM / FISHERS |     P=0.371N     P=0.247      P=0.500      (e)         |P=0.232      (e)          (e)          P=0.515      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    5/50 (10%)   2/50 (4%)    1/49 (2%)   |0/47 (0%)    2/50 (4%)    3/50 (6%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     2.4%         11.0%        5.0%         2.6%        |0.0%         4.6%         6.4%         2.2%         |
|TERMINAL (d)       |     0/28 (0%)    0/32 (0%)    1/27 (4%)    0/28 (0%)   |0/32 (0%)    1/31 (3%)    1/39 (3%)    1/33 (3%)    |
|FIRST INCIDENCE    |     399          522          527          508         |---          727          509          735 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.293N     P=0.124      P=0.486      P=0.748     |P=0.604N     P=0.240      P=0.144      P=0.506      |
|POLY 3             |     P=0.282N     P=0.121      P=0.483      P=0.745     |P=0.592N     P=0.243      P=0.138      P=0.516      |
|POLY 1.5           |     P=0.278N     P=0.113      P=0.489      P=0.747     |P=0.596N     P=0.247      P=0.135      P=0.515      |
|POLY 6             |     P=0.281N     P=0.132      P=0.478      P=0.746     |P=0.587N     P=0.238      P=0.143      P=0.517      |
|LOGISTIC REGRESSION|     P=0.133N     P=0.032 *    P=0.547      P=0.631N    |P=0.641N     P=0.231      P=0.113      P=0.506      |
|COCH-ARM / FISHERS |     P=0.264N     P=0.102      P=0.500      P=0.747     |P=0.603N     P=0.263      P=0.133      P=0.515      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 10
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Tension Lipidosis                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/49 (0%)   |1/47 (2%)    3/50 (6%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |2.4%         6.8%         2.2%         0.0%         |
|TERMINAL (d)       |     0/28 (0%)    0/32 (0%)    0/27 (0%)    0/28 (0%)   |1/32 (3%)    0/31 (0%)    1/39 (3%)    0/33 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |735 (T)      594          735 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.166N     P=0.305      P=0.717N     P=0.494N     |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.163N     P=0.321      P=0.743N     P=0.484N     |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.165N     P=0.324      P=0.745N     P=0.485N     |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.163N     P=0.317      P=0.739N     P=0.483N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.174N     P=0.342      P=0.717N     (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.167N     P=0.332      P=0.737N     P=0.485N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Centrilobular                                                                                                             |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    0/49 (0%)   |0/47 (0%)    0/50 (0%)    1/50 (2%)    3/50 (6%)    |
|POLY-3 ADJUSTED (b)|     4.8%         0.0%         0.0%         0.0%        |0.0%         0.0%         2.2%         6.5%         |
|TERMINAL (d)       |     0/28 (0%)    0/32 (0%)    0/27 (0%)    0/28 (0%)   |0/32 (0%)    0/31 (0%)    0/39 (0%)    0/33 (0%)    |
|FIRST INCIDENCE    |     560          ---          ---          ---         |---          ---          618          645          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.331N     P=0.228N     P=0.267N     P=0.263N    |P=0.031 *    (e)          P=0.518      P=0.141      |
|POLY 3             |     P=0.319N     P=0.229N     P=0.251N     P=0.256N    |P=0.028 *    (e)          P=0.518      P=0.136      |
|POLY 1.5           |     P=0.316N     P=0.232N     P=0.245N     P=0.252N    |P=0.027 *    (e)          P=0.515      P=0.134      |
|POLY 6             |     P=0.320N     P=0.227N     P=0.257N     P=0.259N    |P=0.030 *    (e)          P=0.522      P=0.140      |
|LOGISTIC REGRESSION|     P=0.283N     P=0.266N     P=0.225N     P=0.222N    |P=0.016 *    (e)          P=0.502      P=0.113      |
|COCH-ARM / FISHERS |     P=0.311N     P=0.247N     P=0.247N     P=0.253N    |P=0.026 *    (e)          P=0.515      P=0.133      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 11
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Hemorrhage                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    3/50 (6%)    0/50 (0%)   |0/49 (0%)    1/50 (2%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         7.2%         0.0%        |0.0%         2.3%         0.0%         0.0%         |
|TERMINAL (d)       |     0/28 (0%)    0/32 (0%)    0/27 (0%)    0/28 (0%)   |0/32 (0%)    0/31 (0%)    0/39 (0%)    0/33 (0%)    |
|FIRST INCIDENCE    |     ---          ---          387          ---         |---          483          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.603N     (e)          P=0.120      (e)         |P=0.601N     P=0.517      (e)          (e)          |
|POLY 3             |     P=0.615N     (e)          P=0.119      (e)         |P=0.604N     P=0.508      (e)          (e)          |
|POLY 1.5           |     P=0.606N     (e)          P=0.120      (e)         |P=0.604N     P=0.508      (e)          (e)          |
|POLY 6             |     P=0.620N     (e)          P=0.120      (e)         |P=0.607N     P=0.505      (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.297N     (e)          P=0.129      (e)         |P=0.861N     P=0.289      (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.581N     (e)          P=0.121      (e)         |P=0.607N     P=0.505      (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung: Alveolar Epithelium                                                                                                        |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     5/50 (10%)   6/50 (12%)   4/50 (8%)    3/50 (6%)   |4/49 (8%)    3/50 (6%)    3/50 (6%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     12.1%        13.7%        9.9%         7.6%        |9.4%         6.9%         6.6%         2.2%         |
|TERMINAL (d)       |     4/28 (14%)   5/32 (16%)   2/27 (7%)    3/28 (11%)  |4/32 (13%)   3/31 (10%)   3/39 (8%)    1/33 (3%)    |
|FIRST INCIDENCE    |     664          601          387          733 (T)     |735 (T)      735 (T)      735 (T)      735 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.269N     P=0.584      P=0.531N     P=0.357N    |P=0.144N     P=0.518N     P=0.392N     P=0.169N     |
|POLY 3             |     P=0.276N     P=0.540      P=0.514N     P=0.386N    |P=0.139N     P=0.488N     P=0.460N     P=0.156N     |
|POLY 1.5           |     P=0.265N     P=0.525      P=0.507N     P=0.378N    |P=0.144N     P=0.485N     P=0.470N     P=0.161N     |
|POLY 6             |     P=0.283N     P=0.555      P=0.520N     P=0.389N    |P=0.133N     P=0.499N     P=0.448N     P=0.153N     |
|LOGISTIC REGRESSION|     P=0.265N     P=0.547      P=0.507N     P=0.378N    |P=0.144N     P=0.518N     P=0.392N     P=0.169N     |
|COCH-ARM / FISHERS |     P=0.237N     P=0.500      P=0.500N     P=0.357N    |P=0.153N     P=0.489N     P=0.489N     P=0.175N     |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 12
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mesenteric                                                                                                           |
|     Angiectasis                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/48 (2%)    0/49 (0%)    1/48 (2%)    0/49 (0%)   |1/46 (2%)    2/48 (4%)    0/47 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     2.5%         0.0%         2.6%         0.0%        |2.5%         4.7%         0.0%         0.0%         |
|TERMINAL (d)       |     0/28 (0%)    0/32 (0%)    1/26 (4%)    0/28 (0%)   |1/32 (3%)    0/31 (0%)    0/39 (0%)    0/33 (0%)    |
|FIRST INCIDENCE    |     695          ---          733 (T)      ---         |735 (T)      594          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.496N     P=0.489N     P=0.738      P=0.518N    |P=0.227N     P=0.495      P=0.461N     P=0.494N     |
|POLY 3             |     P=0.495N     P=0.488N     P=0.750      P=0.508N    |P=0.232N     P=0.517      P=0.482N     P=0.481N     |
|POLY 1.5           |     P=0.489N     P=0.490N     P=0.754      P=0.505N    |P=0.231N     P=0.518      P=0.487N     P=0.482N     |
|POLY 6             |     P=0.499N     P=0.485N     P=0.745      P=0.510N    |P=0.234N     P=0.514      P=0.477N     P=0.480N     |
|LOGISTIC REGRESSION|     P=0.493N     P=0.492N     P=0.749      P=0.505N    |P=0.251N     P=0.507      (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.475N     P=0.495N     P=0.753N     P=0.495N    |P=0.232N     P=0.516      P=0.495N     P=0.484N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node: Iliac                                                                                                                |
|     Infiltration Cellular Plasma Cell                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/4 (0%)     1/3 (33%)    2/7 (29%)    1/1 (100%)  |0/7 (0%)     0/2 (0%)     0/5 (0%)     0/4 (0%)     |
|POLY-3 ADJUSTED (b)|     0.0%         33.3%        35.8%        100.0%      |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/2 (0%)     0/2 (0%)     0/0 (0%)     0/0 (0%)    |0/5 (0%)     0/1 (0%)     0/3 (0%)     0/0 (0%)     |
|FIRST INCIDENCE    |     ---          639          499          667         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.542      P=0.520      P=0.240      P=0.494     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.181      P=0.481      P=0.344      P<0.001 **  |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.171      P=0.462      P=0.353      P<0.001 **  |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.197      P=0.512      P=0.321      P=0.002 **  |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.170      P=0.316      P=0.579      P=0.210     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.164      P=0.429      P=0.382      P=0.200     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 13
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery: Fat                                                                                                                   |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/4 (75%)    2/2 (100%)   4/4 (100%)   2/2 (100%)  |7/7 (100%)   6/8 (75%)    6/8 (75%)    10/10 (100%) |
|POLY-3 ADJUSTED (b)|     75.0%        100.0%       100.0%       100.0%      |100.0%       82.4%        76.8%        100.0%       |
|TERMINAL (d)       |     0/1 (0%)     2/2 (100%)   2/2 (100%)   2/2 (100%)  |5/5 (100%)   6/7 (86%)    6/7 (86%)    6/6 (100%)   |
|FIRST INCIDENCE    |     610          733 (T)      387          733 (T)     |639          735 (T)      735 (T)      527          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.367N     P=0.343N     P=0.579      P=0.380N    |P=0.047 *    P=0.152N     P=0.133N     (e)          |
|POLY 3             |     P=0.622      P=0.631      P=0.500      P=0.631     |P=0.339      P=0.400N     P=0.278N     (e)          |
|POLY 1.5           |     P=0.622      P=0.631      P=0.500      P=0.631     |P=0.302      P=0.330N     P=0.266N     (e)          |
|POLY 6             |     P=0.622      P=0.631      P=0.500      P=0.631     |P=0.380      P=0.470N     P=0.303N     (e)          |
|LOGISTIC REGRESSION|     (e)          P=0.343N     (e)          P=0.380N    |P=0.206      P=0.330N     P=0.186N     (e)          |
|COCH-ARM / FISHERS |     P=0.635      P=0.667      P=0.500      P=0.667     |P=0.256      P=0.267N     P=0.267N     (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose                                                                                                                             |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    2/49 (4%)    2/50 (4%)    0/48 (0%)   |0/47 (0%)    1/50 (2%)    1/49 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     2.4%         4.6%         5.0%         0.0%        |0.0%         2.3%         2.2%         0.0%         |
|TERMINAL (d)       |     0/28 (0%)    0/32 (0%)    1/27 (4%)    0/28 (0%)   |0/32 (0%)    1/31 (3%)    0/39 (0%)    0/33 (0%)    |
|FIRST INCIDENCE    |     580          649          480          ---         |---          735 (T)      628          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.259N     P=0.517      P=0.485      P=0.524N    |P=0.511N     P=0.494      P=0.514      (e)          |
|POLY 3             |     P=0.258N     P=0.512      P=0.486      P=0.517N    |P=0.511N     P=0.505      P=0.516      (e)          |
|POLY 1.5           |     P=0.254N     P=0.505      P=0.492      P=0.515N    |P=0.512N     P=0.509      P=0.512      (e)          |
|POLY 6             |     P=0.262N     P=0.521      P=0.480      P=0.518N    |P=0.511N     P=0.501      P=0.521      (e)          |
|LOGISTIC REGRESSION|     P=0.202N     P=0.443      P=0.531      P=0.474N    |P=0.531N     P=0.494      P=0.485      (e)          |
|COCH-ARM / FISHERS |     P=0.241N     P=0.492      P=0.500      P=0.510N    |P=0.514N     P=0.515      P=0.510      (e)          |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 14
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose: Olfactory Epithelium                                                                                                       |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    1/49 (2%)    1/50 (2%)    2/48 (4%)   |0/47 (0%)    1/50 (2%)    0/49 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     2.4%         2.3%         2.5%         5.2%        |0.0%         2.3%         0.0%         0.0%         |
|TERMINAL (d)       |     0/28 (0%)    0/32 (0%)    1/27 (4%)    2/28 (7%)   |0/32 (0%)    0/31 (0%)    0/39 (0%)    0/33 (0%)    |
|FIRST INCIDENCE    |     527          652          733 (T)      733 (T)     |---          639          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.344      P=0.752N     P=0.749      P=0.489     |P=0.594N     P=0.505      (e)          (e)          |
|POLY 3             |     P=0.334      P=0.756N     P=0.748      P=0.470     |P=0.607N     P=0.507      (e)          (e)          |
|POLY 1.5           |     P=0.340      P=0.759N     P=0.753      P=0.474     |P=0.605N     P=0.509      (e)          (e)          |
|POLY 6             |     P=0.329      P=0.751N     P=0.742      P=0.468     |P=0.611N     P=0.503      (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.353      P=0.708      P=0.752N     P=0.488     |P=0.644N     P=0.528      (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.355      P=0.747      P=0.753N     P=0.485     |P=0.603N     P=0.515      (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose: Olfactory Epithelium                                                                                                       |
|     Degeneration Hyaline                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     6/50 (12%)   7/49 (14%)   16/50 (32%)  17/48 (35%) |17/47 (36%)  19/50 (38%)  24/49 (49%)  27/50 (54%)  |
|POLY-3 ADJUSTED (b)|     14.1%        16.3%        39.8%        43.0%       |39.0%        42.4%        52.5%        56.9%        |
|TERMINAL (d)       |     3/28 (11%)   5/32 (16%)   11/27 (41%)  12/28 (43%) |12/32 (38%)  13/31 (42%)  23/39 (59%)  16/33 (49%)  |
|FIRST INCIDENCE    |     580          649          645          508         |449          594          600          583          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.004 **   P=0.577      P=0.013 *    P=0.010 *   |P=0.053      P=0.396      P=0.321      P=0.079      |
|POLY 3             |     P<0.001 **   P=0.509      P=0.006 **   P=0.003 **  |P=0.054      P=0.455      P=0.139      P=0.062      |
|POLY 1.5           |     P=0.002 **   P=0.501      P=0.009 **   P=0.003 **  |P=0.048 *    P=0.477      P=0.139      P=0.060      |
|POLY 6             |     P<0.001 **   P=0.516      P=0.005 **   P=0.002 **  |P=0.067      P=0.429      P=0.144      P=0.071      |
|LOGISTIC REGRESSION|     P=0.002 **   P=0.508      P=0.009 **   P=0.004 **  |P=0.057      P=0.467      P=0.171      P=0.065      |
|COCH-ARM / FISHERS |     P=0.004 **   P=0.484      P=0.014 *    P=0.006 **  |P=0.043 *    P=0.510      P=0.144      P=0.059      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 15
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose: Respiratory Epithelium                                                                                                     |
|     Degeneration Hyaline                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     6/50 (12%)   19/49 (39%)  29/50 (58%)  39/48 (81%) |21/47 (45%)  39/50 (78%)  41/49 (84%)  48/50 (96%)  |
|POLY-3 ADJUSTED (b)|     14.2%        42.1%        68.4%        89.5%       |47.7%        82.3%        86.4%        96.9%        |
|TERMINAL (d)       |     4/28 (14%)   12/32 (38%)  22/27 (82%)  27/28 (96%) |16/32 (50%)  25/31 (81%)  36/39 (92%)  33/33 (100%) |
|FIRST INCIDENCE    |     580          546          387          330         |541          567          477          527          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.010 *    P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P=0.003 **   P<0.001 **   |
|POLY 3             |     P<0.001 **   P=0.003 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 1.5           |     P<0.001 **   P=0.002 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|POLY 6             |     P<0.001 **   P=0.004 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|LOGISTIC REGRESSION|     P<0.001 **   P=0.003 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|COCH-ARM / FISHERS |     P<0.001 **   P=0.002 **   P<0.001 **   P<0.001 **  |P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **   |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Angiectasis                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |0/48 (0%)    1/50 (2%)    0/48 (0%)    3/50 (6%)    |
|POLY-3 ADJUSTED (b)|                                                        |0.0%         2.3%         0.0%         6.6%         |
|TERMINAL (d)       |                                                        |0/32 (0%)    0/31 (0%)    0/38 (0%)    3/33 (9%)    |
|FIRST INCIDENCE    |                                                        |---          615          ---          735 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.043 *    P=0.505      (e)          P=0.126      |
|POLY 3             |                                                        |P=0.045 *    P=0.507      (e)          P=0.133      |
|POLY 1.5           |                                                        |P=0.044 *    P=0.508      (e)          P=0.131      |
|POLY 6             |                                                        |P=0.045 *    P=0.504      (e)          P=0.134      |
|LOGISTIC REGRESSION|                                                        |P=0.044 *    P=0.475      (e)          P=0.126      |
|COCH-ARM / FISHERS |                                                        |P=0.044 *    P=0.510      (e)          P=0.129      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 16
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |13/48 (27%)  14/50 (28%)  11/48 (23%)  8/50 (16%)   |
|POLY-3 ADJUSTED (b)|                                                        |29.9%        31.7%        24.6%        17.0%        |
|TERMINAL (d)       |                                                        |8/32 (25%)   11/31 (36%)  10/38 (26%)  5/33 (15%)   |
|FIRST INCIDENCE    |                                                        |621          611          620          527          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.084N     P=0.473      P=0.262N     P=0.147N     |
|POLY 3             |                                                        |P=0.060N     P=0.517      P=0.377N     P=0.114N     |
|POLY 1.5           |                                                        |P=0.068N     P=0.537      P=0.386N     P=0.120N     |
|POLY 6             |                                                        |P=0.054N     P=0.478      P=0.370N     P=0.111N     |
|LOGISTIC REGRESSION|                                                        |P=0.072N     P=0.526      P=0.367N     P=0.144N     |
|COCH-ARM / FISHERS |                                                        |P=0.084N     P=0.550      P=0.407N     P=0.138N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Basophilic Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/48 (2%)    0/50 (0%)    0/47 (0%)   |1/47 (2%)    2/50 (4%)    0/48 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         2.4%         0.0%         0.0%        |2.4%         4.6%         0.0%         0.0%         |
|TERMINAL (d)       |     0/28 (0%)    1/32 (3%)    0/27 (0%)    0/27 (0%)   |1/32 (3%)    2/31 (7%)    0/39 (0%)    0/33 (0%)    |
|FIRST INCIDENCE    |     ---          733 (T)      ---          ---         |735 (T)      735 (T)      ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.624N     P=0.527      (e)          (e)         |P=0.232N     P=0.489      P=0.461N     P=0.494N     |
|POLY 3             |     P=0.608N     P=0.506      (e)          (e)         |P=0.237N     P=0.509      P=0.490N     P=0.486N     |
|POLY 1.5           |     P=0.611N     P=0.501      (e)          (e)         |P=0.236N     P=0.515      P=0.492N     P=0.488N     |
|POLY 6             |     P=0.604N     P=0.511      (e)          (e)         |P=0.238N     P=0.501      P=0.485N     P=0.484N     |
|LOGISTIC REGRESSION|     (e)          P=0.527      (e)          (e)         |P=0.232N     P=0.489      (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.617N     P=0.490      (e)          (e)         |P=0.237N     P=0.523      P=0.495N     P=0.490N     |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 17
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    4/48 (8%)    3/49 (6%)    4/48 (8%)   |13/49 (27%)  15/49 (31%)  19/49 (39%)  14/49 (29%)  |
|POLY-3 ADJUSTED (b)|     2.4%         9.4%         7.8%         10.2%       |29.7%        34.2%        41.8%        30.5%        |
|TERMINAL (d)       |     1/28 (4%)    4/32 (13%)   2/27 (7%)    3/28 (11%)  |9/32 (28%)   10/31 (32%)  17/39 (44%)  10/33 (30%)  |
|FIRST INCIDENCE    |     733 (T)      733 (T)      708          682         |541          611          620          596          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.272      P=0.220      P=0.291      P=0.178     |P=0.459N     P=0.393      P=0.324      P=0.550      |
|POLY 3             |     P=0.276      P=0.186      P=0.282      P=0.161     |P=0.434N     P=0.408      P=0.163      P=0.557      |
|POLY 1.5           |     P=0.278      P=0.179      P=0.288      P=0.161     |P=0.459N     P=0.417      P=0.156      P=0.541      |
|POLY 6             |     P=0.278      P=0.194      P=0.277      P=0.163     |P=0.412N     P=0.390      P=0.173      P=0.568      |
|LOGISTIC REGRESSION|     P=0.267      P=0.220      P=0.275      P=0.163     |P=0.427N     P=0.420      P=0.179      P=0.547      |
|COCH-ARM / FISHERS |     P=0.291      P=0.168      P=0.301      P=0.168     |P=0.507N     P=0.412      P=0.141      P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Preputial Gland                                                                                                                  |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/48 (0%)    2/50 (4%)    1/50 (2%)   |                                                    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         5.1%         2.5%        |                                                    |
|TERMINAL (d)       |     0/28 (0%)    0/31 (0%)    2/27 (7%)    1/28 (4%)   |                                                    |
|FIRST INCIDENCE    |     ---          ---          733 (T)      733 (T)     |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.408      (e)          P=0.230      P=0.500     |                                                    |
|POLY 3             |     P=0.390      (e)          P=0.227      P=0.490     |                                                    |
|POLY 1.5           |     P=0.399      (e)          P=0.231      P=0.493     |                                                    |
|POLY 6             |     P=0.384      (e)          P=0.223      P=0.490     |                                                    |
|LOGISTIC REGRESSION|     (e)          (e)          P=0.230      P=0.500     |                                                    |
|COCH-ARM / FISHERS |     P=0.424      (e)          P=0.247      P=0.500     |                                                    |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 18
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Preputial Gland                                                                                                                  |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    2/48 (4%)    0/50 (0%)    3/50 (6%)   |                                                    |
|POLY-3 ADJUSTED (b)|     0.0%         4.8%         0.0%         7.6%        |                                                    |
|TERMINAL (d)       |     0/28 (0%)    2/31 (7%)    0/27 (0%)    3/28 (11%)  |                                                    |
|FIRST INCIDENCE    |     ---          733 (T)      ---          733 (T)     |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.096      P=0.261      (e)          P=0.120     |                                                    |
|POLY 3             |     P=0.099      P=0.239      (e)          P=0.109     |                                                    |
|POLY 1.5           |     P=0.100      P=0.235      (e)          P=0.112     |                                                    |
|POLY 6             |     P=0.098      P=0.243      (e)          P=0.109     |                                                    |
|LOGISTIC REGRESSION|     (e)          P=0.261      (e)          P=0.120     |                                                    |
|COCH-ARM / FISHERS |     P=0.107      P=0.237      (e)          P=0.121     |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Prostate                                                                                                                         |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/48 (0%)    2/46 (4%)    4/47 (9%)    4/48 (8%)   |                                                    |
|POLY-3 ADJUSTED (b)|     0.0%         4.8%         10.3%        10.1%       |                                                    |
|TERMINAL (d)       |     0/27 (0%)    0/32 (0%)    0/26 (0%)    0/28 (0%)   |                                                    |
|FIRST INCIDENCE    |     ---          639          628          631         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.103      P=0.263      P=0.062      P=0.062     |                                                    |
|POLY 3             |     P=0.109      P=0.248      P=0.056      P=0.059     |                                                    |
|POLY 1.5           |     P=0.111      P=0.240      P=0.056      P=0.058     |                                                    |
|POLY 6             |     P=0.111      P=0.257      P=0.056      P=0.061     |                                                    |
|LOGISTIC REGRESSION|     P=0.132      P=0.186      P=0.060      P=0.064     |                                                    |
|COCH-ARM / FISHERS |     P=0.122      P=0.237      P=0.056      P=0.059     |                                                    |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 19
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Prepuce                                                                                                                    |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     7/49 (14%)   6/50 (12%)   13/50 (26%)  9/50 (18%)  |0/49 (0%)    0/50 (0%)    0/49 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     16.6%        13.4%        29.3%        20.8%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/27 (0%)    1/32 (3%)    2/27 (7%)    1/28 (4%)   |0/32 (0%)    0/31 (0%)    0/39 (0%)    0/33 (0%)    |
|FIRST INCIDENCE    |     387          562          387          251         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.308      P=0.436N     P=0.108      P=0.367     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.348      P=0.456N     P=0.122      P=0.410     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.352      P=0.467N     P=0.119      P=0.406     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.352      P=0.445N     P=0.128      P=0.419     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.539      P=0.543N     P=0.138      P=0.511     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.371      P=0.484N     P=0.115      P=0.410     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hematopoietic Cell Proliferation                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    3/49 (6%)    5/50 (10%)   4/48 (8%)   |4/49 (8%)    12/50 (24%)  6/50 (12%)   5/50 (10%)   |
|POLY-3 ADJUSTED (b)|     9.5%         7.0%         12.2%        10.0%       |9.2%         26.2%        12.9%        10.6%        |
|TERMINAL (d)       |     0/28 (0%)    2/32 (6%)    1/27 (4%)    0/28 (0%)   |1/32 (3%)    4/31 (13%)   4/39 (10%)   0/33 (0%)    |
|FIRST INCIDENCE    |     608          583          512          508         |541          567          600          527          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.496      P=0.456N     P=0.460      P=0.609     |P=0.237N     P=0.037 *    P=0.463      P=0.540      |
|POLY 3             |     P=0.502      P=0.487N     P=0.484      P=0.614     |P=0.211N     P=0.033 *    P=0.415      P=0.554      |
|POLY 1.5           |     P=0.506      P=0.495N     P=0.490      P=0.613     |P=0.224N     P=0.032 *    P=0.404      P=0.540      |
|POLY 6             |     P=0.505      P=0.480N     P=0.480      P=0.621     |P=0.201N     P=0.033 *    P=0.428      P=0.565      |
|LOGISTIC REGRESSION|     P=0.558      P=0.516N     P=0.511      P=0.637     |P=0.331N     P=0.027 *    P=0.347      P=0.389      |
|COCH-ARM / FISHERS |     P=0.526      P=0.511N     P=0.500      P=0.619     |P=0.253N     P=0.030 *    P=0.383      P=0.513      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 20
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/49 (0%)    1/50 (2%)    1/48 (2%)   |2/48 (4%)    4/49 (8%)    1/49 (2%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     4.8%         0.0%         2.5%         2.6%        |4.7%         9.2%         2.2%         2.2%         |
|TERMINAL (d)       |     1/28 (4%)    0/32 (0%)    1/27 (4%)    1/28 (4%)   |0/32 (0%)    1/31 (3%)    1/39 (3%)    1/33 (3%)    |
|FIRST INCIDENCE    |     695          ---          733 (T)      733 (T)     |608          649          735 (T)      735 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.675N     P=0.216N     P=0.523N     P=0.511N    |P=0.233N     P=0.329      P=0.460N     P=0.482N     |
|POLY 3             |     P=0.675      P=0.227N     P=0.517N     P=0.527N    |P=0.240N     P=0.345      P=0.481N     P=0.484N     |
|POLY 1.5           |     P=0.680N     P=0.232N     P=0.510N     P=0.524N    |P=0.241N     P=0.348      P=0.485N     P=0.486N     |
|POLY 6             |     P=0.670      P=0.223N     P=0.524N     P=0.527N    |P=0.241N     P=0.339      P=0.476N     P=0.485N     |
|LOGISTIC REGRESSION|     P=0.684N     P=0.223N     P=0.523N     P=0.523N    |P=0.254N     P=0.336      P=0.516N     P=0.516N     |
|COCH-ARM / FISHERS |     P=0.665N     P=0.253N     P=0.500N     P=0.515N    |P=0.245N     P=0.349      P=0.492N     P=0.492N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Inflammation Acute                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/49 (0%)    1/50 (2%)    1/48 (2%)   |1/48 (2%)    2/49 (4%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         2.5%         2.6%        |2.4%         4.6%         0.0%         0.0%         |
|TERMINAL (d)       |     0/28 (0%)    0/32 (0%)    1/27 (4%)    1/28 (4%)   |0/32 (0%)    1/31 (3%)    0/39 (0%)    0/33 (0%)    |
|FIRST INCIDENCE    |     ---          ---          733 (T)      733 (T)     |709          731          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.336      (e)          P=0.493      P=0.500     |P=0.230N     P=0.486      P=0.479N     P=0.484N     |
|POLY 3             |     P=0.319      (e)          P=0.491      P=0.486     |P=0.236N     P=0.505      P=0.487N     P=0.489N     |
|POLY 1.5           |     P=0.325      (e)          P=0.495      P=0.487     |P=0.236N     P=0.508      P=0.490N     P=0.491N     |
|POLY 6             |     P=0.316      (e)          P=0.488      P=0.486     |P=0.238N     P=0.499      P=0.483N     P=0.488N     |
|LOGISTIC REGRESSION|     (e)          (e)          P=0.493      P=0.500     |P=0.228N     P=0.497      P=0.493N     P=0.493N     |
|COCH-ARM / FISHERS |     P=0.340      (e)          P=0.500      P=0.490     |P=0.238N     P=0.508      P=0.495N     P=0.495N     |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 21
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Glandular                                                                                                               |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    2/47 (4%)    1/49 (2%)    0/46 (0%)   |0/46 (0%)    0/48 (0%)    1/48 (2%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         4.7%         2.5%         0.0%        |0.0%         0.0%         2.2%         0.0%         |
|TERMINAL (d)       |     0/28 (0%)    0/32 (0%)    0/27 (0%)    0/28 (0%)   |0/32 (0%)    0/31 (0%)    0/39 (0%)    0/33 (0%)    |
|FIRST INCIDENCE    |     ---          601          389          ---         |---          ---          509          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.387N     P=0.253      P=0.500      (e)         |P=0.762N     (e)          P=0.513      (e)          |
|POLY 3             |     P=0.383N     P=0.247      P=0.496      (e)         |P=0.762N     (e)          P=0.516      (e)          |
|POLY 1.5           |     P=0.383N     P=0.240      P=0.498      (e)         |P=0.763N     (e)          P=0.513      (e)          |
|POLY 6             |     P=0.381N     P=0.256      P=0.494      (e)         |P=0.760N     (e)          P=0.522      (e)          |
|LOGISTIC REGRESSION|     P=0.241N     P=0.160      P=0.581      (e)         |P=0.879      (e)          P=0.476      (e)          |
|COCH-ARM / FISHERS |     P=0.378N     P=0.237      P=0.500      (e)         |P=0.766N     (e)          P=0.511      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     5/50 (10%)   6/50 (12%)   3/50 (6%)    3/49 (6%)   |25/48 (52%)  16/50 (32%)  29/49 (59%)  30/50 (60%)  |
|POLY-3 ADJUSTED (b)|     12.0%        13.6%        7.6%         7.8%        |57.5%        36.1%        62.1%        63.4%        |
|TERMINAL (d)       |     3/28 (11%)   3/32 (9%)    3/27 (11%)   3/28 (11%)  |20/32 (63%)  11/31 (36%)  25/39 (64%)  22/33 (67%)  |
|FIRST INCIDENCE    |     653          512          733 (T)      733 (T)     |610          615          477          583          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.282N     P=0.575      P=0.391N     P=0.369N    |P=0.062      P=0.072N     P=0.509N     P=0.298      |
|POLY 3             |     P=0.295N     P=0.542      P=0.386N     P=0.400N    |P=0.070      P=0.032N*    P=0.407      P=0.358      |
|POLY 1.5           |     P=0.284N     P=0.527      P=0.374N     P=0.392N    |P=0.059      P=0.030N*    P=0.371      P=0.331      |
|POLY 6             |     P=0.302N     P=0.557      P=0.401N     P=0.405N    |P=0.088      P=0.036N*    P=0.447      P=0.387      |
|LOGISTIC REGRESSION|     P=0.294N     P=0.523      P=0.390N     P=0.391N    |P=0.075      P=0.041N*    P=0.408      P=0.359      |
|COCH-ARM / FISHERS |     P=0.257N     P=0.500      P=0.357N     P=0.369N    |P=0.047 *    P=0.035N*    P=0.309      P=0.279      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 22
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Tooth                                                                                                                            |
|     Malformation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     6/7 (86%)    12/14 (86%)  7/9 (78%)    14/16 (88%) |0/0 (0%)     0/0 (0%)     1/1 (100%)   1/1 (100%)   |
|POLY-3 ADJUSTED (b)|     94.2%        89.6%        77.8%        87.5%       |0.0%         0.0%         100.0%       100.0%       |
|TERMINAL (d)       |     4/4 (100%)   12/12 (100%) 5/7 (71%)    12/14 (86%) |0/0 (0%)     0/0 (0%)     1/1 (100%)   0/0 (0%)     |
|FIRST INCIDENCE    |     592          733 (T)      480          670         |---          ---          735 (T)      596          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.585N     P=0.224N     P=0.455N     P=0.540N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.614N     P=0.723N     P=0.437N     P=0.616N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.626      P=0.719N     P=0.502N     P=0.690N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.533N     P=0.790N     P=0.367N     P=0.528N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.626N     P=0.171N     P=0.570N     P=0.513N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.534      P=0.726      P=0.600N     P=0.684     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Urinary Bladder                                                                                                                  |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/49 (8%)    3/47 (6%)    7/49 (14%)   6/46 (13%)  |0/45 (0%)    0/49 (0%)    0/49 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     9.4%         7.1%         16.7%        15.2%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/28 (0%)    1/32 (3%)    0/27 (0%)    0/28 (0%)   |0/31 (0%)    0/31 (0%)    0/39 (0%)    0/33 (0%)    |
|FIRST INCIDENCE    |     399          639          499          457         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.245      P=0.464N     P=0.243      P=0.350     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.221      P=0.501N     P=0.252      P=0.320     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.227      P=0.508N     P=0.255      P=0.322     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.221      P=0.494N     P=0.251      P=0.325     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.316      P=0.651      P=0.299      P=0.358     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.244      P=0.524N     P=0.262      P=0.330     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 04                                            Page 23
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Hydrometra                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |6/49 (12%)   7/50 (14%)   3/50 (6%)    4/50 (8%)    |
|POLY-3 ADJUSTED (b)|                                                        |13.9%        15.6%        6.5%         8.7%         |
|TERMINAL (d)       |                                                        |5/32 (16%)   3/31 (10%)   2/39 (5%)    4/33 (12%)   |
|FIRST INCIDENCE    |                                                        |541          572          628          735 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.257N     P=0.491      P=0.171N     P=0.347N     |
|POLY 3             |                                                        |P=0.256N     P=0.531      P=0.209N     P=0.331N     |
|POLY 1.5           |                                                        |P=0.260N     P=0.529      P=0.217N     P=0.338N     |
|POLY 6             |                                                        |P=0.255N     P=0.529      P=0.199N     P=0.328N     |
|LOGISTIC REGRESSION|                                                        |P=0.274N     P=0.512      P=0.228N     P=0.326N     |
|COCH-ARM / FISHERS |                                                        |P=0.271N     P=0.516      P=0.233N     P=0.357N     |
|=================================================================================================================================|

(a)  Number of tumor-bearing animals /  number of animals examined at site.
(b)  Poly-3 adjusted lifetime tumor incidence.
(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.
Logistic regression is an alternative
 method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage
and Fishers 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).