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TDMS Study 88070-03 Pathology Tables

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

EXPERIMENT: 88070 TEST: 03                                                                                     TIME: 09:50:34
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:
CONT: N01-ES-15313                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C88070
PATHOLOGIST: GRUMBEIN, S.                                                                                      CAS: 115-11-0007
                

Rats(FISCHER344)
-----------------------------
FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE BASED ON NUMBER OF TISSUES EXAMINED.
IN OTHER TISSUES/ORGANS, RATES ARE BASED ON NUMBER OF ANIMALS NECROPSIED.

                                                 ----------------
                                                 Adrenal Gland
                                                 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: 03                                                                                     TIME: 09:50:34     
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:              
CONT: N01-ES-15313                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C88070     
PATHOLOGIST: GRUMBEIN, S.                                                                                      CAS: 115-11-0007   



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

Male Rats
------------
Organ                                 Morphology
-----                                 ----------
Adrenal Medulla                        Hyperplasia
Heart: Atrium                          Thrombosis
Islets, Pancreatic                     Hyperplasia
Liver                                  Cyst
                                       Regeneration
Lung                                   Inflammation Granulomatous
Mammary Gland                          Galactocele
Nose: Olfactory Epithelium             Degeneration Hyaline
                                       Metaplasia
Skin                                   Inflammation Chronic
Stomach, Forestomach                   Necrosis
Testes                                 Atrophy
Thyroid Gland: C-Cell                  Hyperplasia
===============================================================
Female Rats
------------
Organ                                  Morphology
-----                                  ----------
Adrenal Cortex                         Hyperplasia
Bone                                   Hyperostosis
Intestine Large, Colon                 Parasite Metazoan
Kidney                                 Nephropathy
Larynx: Epiglottis                     Metaplasia
Liver: Centrilobular                   Necrosis
Mesentery: Artery                      Inflammation Chronic
Nose: Lateral Wall                     Metaplasia
Nose: Olfactory Epithelium             Degeneration Hyaline
Ovary                                  Cyst
Pancreas                               Atrophy
Spleen                                 Fibrosis
Testes: Artery                         Inflammation Chronic
===============================================================
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 1
                     Statistical Analysis of Non-neoplastic Lesions in        Rats(FISCHER344)  -                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                                                                                                                   |
|     Degeneration Cystic                                                                                                         |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/49 (0%)    0/50 (0%)    1/50 (2%)   |2/50 (4%)    2/50 (4%)    4/49 (8%)    2/49 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         2.8%        |5.0%         5.5%         9.3%         5.1%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     1/8 (13%)   |1/23 (4%)    2/19 (11%)   4/33 (12%)   1/22 (5%)    |
|FIRST INCIDENCE    |     ---          ---          ---          733 (T)     |715          733 (T)      733 (T)      720          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.280      (e)          (e)          P=0.527     |P=0.589N     P=0.624      P=0.498      P=0.667      |
|POLY 3             |     P=0.245      (e)          (e)          P=0.513     |P=0.567N     P=0.664      P=0.373      P=0.687      |
|POLY 1.5           |     P=0.239      (e)          (e)          P=0.508     |P=0.572N     P=0.673      P=0.355      P=0.685      |
|POLY 6             |     P=0.252      (e)          (e)          P=0.518     |P=0.569N     P=0.651      P=0.394      P=0.683      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.527     |P=0.599N     P=0.632      P=0.438      P=0.671      |
|COCH-ARM / FISHERS |     P=0.229      (e)          (e)          P=0.500     |P=0.580N     P=0.691N     P=0.329      P=0.684      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     21/50 (42%)  23/49 (47%)  24/50 (48%)  23/50 (46%) |15/50 (30%)  16/50 (32%)  24/49 (49%)  21/49 (43%)  |
|POLY-3 ADJUSTED (b)|     55.0%        59.3%        62.6%        55.3%       |35.9%        41.2%        52.3%        51.0%        |
|TERMINAL (d)       |     3/7 (43%)    3/5 (60%)    4/6 (67%)    4/8 (50%)   |11/23 (48%)  9/19 (47%)   16/33 (49%)  15/22 (68%)  |
|FIRST INCIDENCE    |     539          482          500          505         |440          455          399          500          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.290N     P=0.176      P=0.161      P=0.560N    |P=0.139      P=0.293      P=0.319      P=0.107      |
|POLY 3             |     P=0.448N     P=0.431      P=0.311      P=0.582     |P=0.148      P=0.397      P=0.088      P=0.115      |
|POLY 1.5           |     P=0.517N     P=0.405      P=0.325      P=0.514     |P=0.144      P=0.425      P=0.065      P=0.117      |
|POLY 6             |     P=0.371N     P=0.462      P=0.293      P=0.555N    |P=0.142      P=0.367      P=0.125      P=0.107      |
|LOGISTIC REGRESSION|     P=0.439N     P=0.303      P=0.207      P=0.549     |P=0.152      P=0.398      P=0.059      P=0.123      |
|COCH-ARM / FISHERS |     P=0.488      P=0.385      P=0.344      P=0.420     |P=0.142      P=0.500      P=0.042 *    P=0.131      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 2
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                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                                                                                                                   |
|     Hypertrophy                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     7/50 (14%)   6/49 (12%)   7/50 (14%)   4/50 (8%)   |11/50 (22%)  8/50 (16%)   9/49 (18%)   9/49 (18%)   |
|POLY-3 ADJUSTED (b)|     19.8%        18.8%        20.5%        10.9%       |26.4%        21.4%        20.5%        22.9%        |
|TERMINAL (d)       |     2/7 (29%)    2/5 (40%)    1/6 (17%)    1/8 (13%)   |4/23 (17%)   5/19 (26%)   7/33 (21%)   7/22 (32%)   |
|FIRST INCIDENCE    |     552          624          352          576         |390          565          607          668          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.133N     P=0.569      P=0.498      P=0.221N    |P=0.520N     P=0.480N     P=0.191N     P=0.454N     |
|POLY 3             |     P=0.163N     P=0.584N     P=0.593      P=0.231N    |P=0.519N     P=0.399N     P=0.350N     P=0.455N     |
|POLY 1.5           |     P=0.185N     P=0.552N     P=0.604      P=0.242N    |P=0.517N     P=0.369N     P=0.379N     P=0.445N     |
|POLY 6             |     P=0.140N     P=0.619      P=0.574      P=0.226N    |P=0.535N     P=0.442N     P=0.319N     P=0.482N     |
|LOGISTIC REGRESSION|     P=0.196N     P=0.591N     P=0.597N     P=0.233N    |P=0.499N     P=0.367N     P=0.379N     P=0.424N     |
|COCH-ARM / FISHERS |     P=0.221N     P=0.516N     P=0.613N     P=0.262N    |P=0.517N     P=0.306N     P=0.421N     P=0.421N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/49 (2%)    1/50 (2%)    0/50 (0%)   |2/50 (4%)    0/50 (0%)    3/49 (6%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     0.0%         3.2%         3.2%         0.0%        |4.9%         0.0%         6.8%         2.5%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     ---          702          585          ---         |529          ---          552          469          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.502N     P=0.403      P=0.475      (e)         |P=0.573N     P=0.278N     P=0.568      P=0.506N     |
|POLY 3             |     P=0.502N     P=0.484      P=0.487      (e)         |P=0.545N     P=0.260N     P=0.537      P=0.507N     |
|POLY 1.5           |     P=0.509N     P=0.489      P=0.493      (e)         |P=0.554N     P=0.252N     P=0.519      P=0.508N     |
|POLY 6             |     P=0.496N     P=0.474      P=0.479      (e)         |P=0.540N     P=0.270N     P=0.559      P=0.511N     |
|LOGISTIC REGRESSION|     P=0.506N     P=0.446      P=0.516      (e)         |P=0.569N     P=0.221N     P=0.415      P=0.464N     |
|COCH-ARM / FISHERS |     P=0.520N     P=0.495      P=0.500      (e)         |P=0.572N     P=0.247N     P=0.490      P=0.508N     |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 3
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                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)        |     0/50 (0%)    1/49 (2%)    3/50 (6%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/49 (0%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     0.0%         3.2%         9.4%         0.0%        |0.0%         0.0%         0.0%         2.5%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     ---          684          516          ---         |---          ---          ---          642          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.386N     P=0.459      P=0.110      (e)         |P=0.231      (e)          (e)          P=0.495      |
|POLY 3             |     P=0.396N     P=0.484      P=0.108      (e)         |P=0.232      (e)          (e)          P=0.497      |
|POLY 1.5           |     P=0.411N     P=0.489      P=0.113      (e)         |P=0.230      (e)          (e)          P=0.496      |
|POLY 6             |     P=0.381N     P=0.475      P=0.102      (e)         |P=0.234      (e)          (e)          P=0.497      |
|LOGISTIC REGRESSION|     P=0.432N     P=0.463      P=0.124      (e)         |P=0.226      (e)          (e)          P=0.499      |
|COCH-ARM / FISHERS |     P=0.435N     P=0.495      P=0.121      (e)         |P=0.225      (e)          (e)          P=0.495      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     15/50 (30%)  19/49 (39%)  30/50 (60%)  18/50 (36%) |10/50 (20%)  5/50 (10%)   6/49 (12%)   10/49 (20%)  |
|POLY-3 ADJUSTED (b)|     39.7%        49.6%        70.7%        44.2%       |24.1%        13.5%        13.8%        24.9%        |
|TERMINAL (d)       |     1/7 (14%)    1/5 (20%)    3/6 (50%)    4/8 (50%)   |5/23 (22%)   2/19 (11%)   5/33 (15%)   6/22 (27%)   |
|FIRST INCIDENCE    |     516          523          453          534         |552          662          626          580          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.270N     P=0.131      P=0.003 **   P=0.442     |P=0.253      P=0.233N     P=0.084N     P=0.555      |
|POLY 3             |     P=0.370N     P=0.250      P=0.002 **   P=0.427     |P=0.271      P=0.180N     P=0.173N     P=0.569      |
|POLY 1.5           |     P=0.417N     P=0.241      P=0.002 **   P=0.391     |P=0.265      P=0.162N     P=0.189N     P=0.570      |
|POLY 6             |     P=0.348N     P=0.267      P=0.004 **   P=0.457     |P=0.270      P=0.207N     P=0.158N     P=0.554      |
|LOGISTIC REGRESSION|     P=0.497N     P=0.226      P=0.002 **   P=0.377     |P=0.261      P=0.168N     P=0.178N     P=0.576      |
|COCH-ARM / FISHERS |     P=0.507N     P=0.240      P=0.002 **   P=0.335     |P=0.252      P=0.131N     P=0.220N     P=0.579      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 4
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Blood Vessel: Aorta                                                                                                              |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/2 (100%)   2/2 (100%)   2/2 (100%)   2/2 (100%)  |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     |
|POLY-3 ADJUSTED (b)|     100.0%       100.0%       100.0%       100.0%      |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/0 (0%)     1/1 (100%)   0/0 (0%)     1/1 (100%)  |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     |
|FIRST INCIDENCE    |     639          684          480          700         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Fibrous Osteodystrophy                                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     9/50 (18%)   7/50 (14%)   9/50 (18%)   6/50 (12%)  |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     25.3%        21.5%        27.1%        16.4%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     1/5 (20%)    1/6 (17%)    2/8 (25%)   |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     539          624          558          664         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.180N     P=0.580      P=0.405      P=0.277N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.216N     P=0.465N     P=0.544      P=0.257N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.244N     P=0.433N     P=0.572      P=0.266N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.195N     P=0.521N     P=0.502      P=0.260N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.178N     P=0.491N     P=0.508      P=0.224N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.293N     P=0.393N     P=0.602N     P=0.288N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 5
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Hyperostosis                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    1/50 (2%)   |9/50 (18%)   7/50 (14%)   11/50 (22%)  15/50 (30%)  |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         3.2%         2.8%        |22.1%        18.7%        24.2%        36.1%        |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |6/23 (26%)   4/19 (21%)   7/33 (21%)   7/22 (32%)   |
|FIRST INCIDENCE    |     ---          ---          568          688         |608          580          534          547          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.423      (e)          P=0.484      P=0.547     |P=0.036 *    P=0.545N     P=0.522N     P=0.111      |
|POLY 3             |     P=0.382      (e)          P=0.487      P=0.514     |P=0.046 *    P=0.463N     P=0.512      P=0.121      |
|POLY 1.5           |     P=0.369      (e)          P=0.493      P=0.509     |P=0.042 *    P=0.442N     P=0.468      P=0.117      |
|POLY 6             |     P=0.398      (e)          P=0.479      P=0.520     |P=0.049 *    P=0.493N     P=0.560      P=0.125      |
|LOGISTIC REGRESSION|     P=0.349      (e)          P=0.522      P=0.517     |P=0.038 *    P=0.481N     P=0.468      P=0.109      |
|COCH-ARM / FISHERS |     P=0.348      (e)          P=0.500      P=0.500     |P=0.040 *    P=0.393N     P=0.402      P=0.121      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone Marrow                                                                                                                      |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/48 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    1/50 (2%)    0/49 (0%)    2/49 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |2.5%         2.7%         0.0%         5.1%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    1/19 (5%)    0/33 (0%)    1/22 (5%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |720          733 (T)      ---          692          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.302      P=0.705      P=0.454N     P=0.474      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.314      P=0.742      P=0.485N     P=0.493      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.313      P=0.748      P=0.492N     P=0.492      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.311      P=0.734      P=0.476N     P=0.490      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.308      P=0.726      P=0.472N     P=0.485      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.312      P=0.753N     P=0.505N     P=0.492      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 6
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral Gland                                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |1/50 (2%)    0/49 (0%)    5/47 (11%)   1/48 (2%)    |
|POLY-3 ADJUSTED (b)|                                                        |2.5%         0.0%         11.9%        2.7%         |
|TERMINAL (d)       |                                                        |1/23 (4%)    0/18 (0%)    4/31 (13%)   1/22 (5%)    |
|FIRST INCIDENCE    |                                                        |733 (T)      ---          644          733 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.626N     P=0.549N     P=0.176      P=0.753      |
|POLY 3             |                                                        |P=0.620N     P=0.522N     P=0.112      P=0.747      |
|POLY 1.5           |                                                        |P=0.626N     P=0.517N     P=0.102      P=0.748      |
|POLY 6             |                                                        |P=0.621N     P=0.530N     P=0.125      P=0.743      |
|LOGISTIC REGRESSION|                                                        |P=0.641      (e)          P=0.123      P=0.753      |
|COCH-ARM / FISHERS |                                                        |P=0.636N     P=0.505N     P=0.088      P=0.742      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Esophagus                                                                                                                        |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    2/50 (4%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     3.0%         3.2%         6.3%         0.0%        |0.0%         0.0%         2.3%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     666          670          555          ---         |---          ---          651          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.281N     P=0.707      P=0.451      P=0.491N    |P=0.771N     (e)          P=0.532      (e)          |
|POLY 3             |     P=0.285N     P=0.744      P=0.481      P=0.488N    |P=0.768N     (e)          P=0.521      (e)          |
|POLY 1.5           |     P=0.298N     P=0.751      P=0.490      P=0.492N    |P=0.769N     (e)          P=0.513      (e)          |
|POLY 6             |     P=0.273N     P=0.732      P=0.469      P=0.486N    |P=0.769N     (e)          P=0.531      (e)          |
|LOGISTIC REGRESSION|     P=0.324N     P=0.736      P=0.517      P=0.487N    |P=0.772N     (e)          P=0.476      (e)          |
|COCH-ARM / FISHERS |     P=0.317N     P=0.753N     P=0.500      P=0.500N    |P=0.772N     (e)          P=0.500      (e)          |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 7
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Eye                                                                                                                              |
|     Cataract                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/3 (67%)    0/0 (0%)     3/4 (75%)    0/0 (0%)    |4/4 (100%)   3/4 (75%)    6/6 (100%)   4/4 (100%)   |
|POLY-3 ADJUSTED (b)|     75.1%        0.0%         83.6%        0.0%        |100.0%       84.3%        100.0%       100.0%       |
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     1/1 (100%)   0/0 (0%)    |0/0 (0%)     1/1 (100%)   5/5 (100%)   2/2 (100%)   |
|FIRST INCIDENCE    |     691          ---          650          ---         |440          440          680          630          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.265N    (e)           P=0.597      (e)         |P=0.435N     P=0.385N     (e)          (e)          |
|POLY 3             |     P=1.000N    (e)           P=0.776      (e)         |P=0.876      P=0.757N     (e)          (e)          |
|POLY 1.5           |     P=1.000N    (e)           P=0.732      (e)         |P=0.753      P=0.617N     (e)          (e)          |
|POLY 6             |     P=1.000N    (e)           P=0.882      (e)         |P=0.995      P=0.974N     (e)          (e)          |
|LOGISTIC REGRESSION|     (e)         (e)           (e)          (e)         |P=0.745      P=0.537N     (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.989     (e)           P=0.714      (e)         |P=0.626      P=0.500N     (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Eye                                                                                                                              |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/3 (0%)     0/0 (0%)     2/4 (50%)    0/0 (0%)    |0/4 (0%)     0/4 (0%)     0/6 (0%)     0/4 (0%)     |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         54.1%        0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/1 (0%)     0/0 (0%)    |0/0 (0%)     0/1 (0%)     0/5 (0%)     0/2 (0%)     |
|FIRST INCIDENCE    |     ---          ---          614          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.598N     (e)          P=0.176      (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=1.000N     (e)          P=0.299      (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=1.000N     (e)          P=0.284      (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=1.000N     (e)          P=0.332      (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.883      (e)          P=0.286      (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.861      (e)          P=0.286      (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 8
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Eye: Retina                                                                                                                      |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/3 (33%)    0/0 (0%)     3/4 (75%)    0/0 (0%)    |3/4 (75%)    3/4 (75%)    6/6 (100%)   4/4 (100%)   |
|POLY-3 ADJUSTED (b)|     38.4%        0.0%         83.6%        0.0%        |86.3%        84.3%        100.0%       100.0%       |
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     1/1 (100%)   0/0 (0%)    |0/0 (0%)     1/1 (100%)   5/5 (100%)   2/2 (100%)   |
|FIRST INCIDENCE    |     691          ---          650          ---         |440          440          680          630          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.412N     (e)          P=0.415      (e)         |P=0.549N     P=0.544N     P=0.263N     P=0.511N     |
|POLY 3             |     P=1.000N     (e)          P=0.373      (e)         |P=0.621      P=0.868N     P=0.795      P=0.830      |
|POLY 1.5           |     P=1.000N     (e)          P=0.374      (e)         |P=0.465      P=0.809N     P=0.584      P=0.652      |
|POLY 6             |     P=1.000N     (e)          P=0.382      (e)         |P=0.940      P=0.976N     P=0.999      P=0.998      |
|LOGISTIC REGRESSION|     P=0.896      (e)          P=0.316      (e)         |P=0.503      P=0.781      P=0.821      P=0.752      |
|COCH-ARM / FISHERS |     P=0.887      (e)          P=0.371      (e)         |P=0.344      P=0.786N     P=0.400      P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart                                                                                                                            |
|     Cardiomyopathy                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     39/50 (78%)  39/50 (78%)  41/50 (82%)  41/50 (82%) |30/50 (60%)  29/50 (58%)  37/49 (76%)  31/50 (62%)  |
|POLY-3 ADJUSTED (b)|     86.8%        88.2%        90.7%        86.0%       |69.4%        69.7%        82.8%        73.2%        |
|TERMINAL (d)       |     6/7 (86%)    5/5 (100%)   6/6 (100%)   7/8 (88%)   |19/23 (83%)  13/19 (68%)  30/33 (91%)  20/22 (91%)  |
|FIRST INCIDENCE    |     379          389          453          490         |440          455          620          547          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.225N     P=0.190      P=0.165      P=0.467N    |P=0.441      P=0.306      P=0.332N     P=0.395      |
|POLY 3             |     P=0.447N     P=0.556      P=0.377      P=0.589N    |P=0.466      P=0.588      P=0.090      P=0.438      |
|POLY 1.5           |     P=0.577      P=0.557      P=0.381      P=0.557     |P=0.479      P=0.589      P=0.081      P=0.448      |
|POLY 6             |     P=0.280N     P=0.572      P=0.380      P=0.489N    |P=0.426      P=0.593      P=0.107      P=0.411      |
|LOGISTIC REGRESSION|     P=0.570      P=0.466      P=0.290      P=0.484     |P=0.554      P=0.498      P=0.234      P=0.480      |
|COCH-ARM / FISHERS |     P=0.359      P=0.595N     P=0.402      P=0.402     |P=0.505      P=0.500N     P=0.075      P=0.500      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 9
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart: Artery                                                                                                                    |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    4/50 (8%)    4/50 (8%)    5/50 (10%)  |0/50 (0%)    0/50 (0%)    0/49 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     8.8%         12.7%        12.5%        13.8%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     1/5 (20%)    0/6 (0%)     2/8 (25%)   |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     639          664          480          667         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.468      P=0.355      P=0.397      P=0.400     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.407      P=0.457      P=0.464      P=0.389     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.381      P=0.475      P=0.481      P=0.377     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.434      P=0.426      P=0.435      P=0.396     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.460      P=0.403      P=0.446      P=0.400     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.341      P=0.500      P=0.500      P=0.357     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart: Atrium                                                                                                                    |
|     Thrombosis                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    3/50 (6%)    6/50 (12%)  |0/50 (0%)    0/50 (0%)    1/49 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         3.2%         9.5%         16.4%       |0.0%         0.0%         2.3%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     2/8 (25%)   |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     ---          692          650          670         |---          ---          626          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.019 *    P=0.433      P=0.096      P=0.026 *   |P=0.764N     (e)          P=0.525      (e)          |
|POLY 3             |     P=0.007 **   P=0.485      P=0.106      P=0.018 *   |P=0.767N     (e)          P=0.517      (e)          |
|POLY 1.5           |     P=0.006 **   P=0.491      P=0.112      P=0.017 *   |P=0.768N     (e)          P=0.509      (e)          |
|POLY 6             |     P=0.008 **   P=0.475      P=0.099      P=0.019 *   |P=0.768N     (e)          P=0.528      (e)          |
|LOGISTIC REGRESSION|     P=0.012 *    P=0.456      P=0.098      P=0.019 *   |P=0.769N     (e)          P=0.453      (e)          |
|COCH-ARM / FISHERS |     P=0.005 **   P=0.500      P=0.121      P=0.013 *   |P=0.771N     (e)          P=0.495      (e)          |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 10
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large, Cecum                                                                                                           |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/48 (0%)    0/47 (0%)    2/49 (4%)    1/49 (2%)   |0/48 (0%)    0/49 (0%)    0/48 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         6.6%         2.8%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     ---          ---          620          688         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.494      (e)          P=0.212      P=0.547     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.462      (e)          P=0.221      P=0.517     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.448      (e)          P=0.231      P=0.512     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.478      (e)          P=0.208      P=0.521     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.465      (e)          P=0.212      P=0.518     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.427      (e)          P=0.253      P=0.505     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large, Cecum                                                                                                           |
|     Parasite Metazoan                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/48 (6%)    2/47 (4%)    6/49 (12%)   4/49 (8%)   |5/48 (10%)   2/49 (4%)    4/48 (8%)    3/49 (6%)    |
|POLY-3 ADJUSTED (b)|     9.1%         6.6%         18.9%        11.1%       |12.6%        5.6%         9.4%         7.5%         |
|TERMINAL (d)       |     2/7 (29%)    1/5 (20%)    2/6 (33%)    2/8 (25%)   |2/23 (9%)    2/19 (11%)   4/33 (12%)   0/22 (0%)    |
|FIRST INCIDENCE    |     648          641          500          610         |488          733 (T)      733 (T)      407          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.578      P=0.622N     P=0.167      P=0.580     |P=0.487N     P=0.283N     P=0.334N     P=0.382N     |
|POLY 3             |     P=0.509      P=0.536N     P=0.216      P=0.551     |P=0.441N     P=0.255N     P=0.457N     P=0.352N     |
|POLY 1.5           |     P=0.476      P=0.523N     P=0.233      P=0.535     |P=0.448N     P=0.239N     P=0.473N     P=0.350N     |
|POLY 6             |     P=0.552      P=0.561N     P=0.193      P=0.567     |P=0.443N     P=0.278N     P=0.440N     P=0.365N     |
|LOGISTIC REGRESSION|     P=0.516      P=0.610N     P=0.186      P=0.550     |P=0.464N     P=0.219N     P=0.499N     P=0.331N     |
|COCH-ARM / FISHERS |     P=0.430      P=0.510N     P=0.254      P=0.512     |P=0.466N     P=0.209N     P=0.500N     P=0.346N     |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 11
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large, Colon                                                                                                           |
|     Parasite Metazoan                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/49 (8%)    1/48 (2%)    2/48 (4%)    2/49 (4%)   |5/49 (10%)   0/50 (0%)    1/49 (2%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     12.0%        3.2%         6.6%         5.7%        |12.4%        0.0%         2.3%         2.6%         |
|TERMINAL (d)       |     3/7 (43%)    0/5 (0%)     0/6 (0%)     2/8 (25%)   |0/23 (0%)    0/19 (0%)    1/33 (3%)    1/22 (5%)    |
|FIRST INCIDENCE    |     648          641          585          733 (T)     |488          ---          733 (T)      733 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.362N     P=0.259N     P=0.425N     P=0.252N    |P=0.264N     P=0.058N     P=0.069N     P=0.127N     |
|POLY 3             |     P=0.435N     P=0.199N     P=0.383N     P=0.308N    |P=0.238N     P=0.038N*    P=0.085N     P=0.107N     |
|POLY 1.5           |     P=0.458N     P=0.193N     P=0.366N     P=0.319N    |P=0.244N     P=0.035N*    P=0.091N     P=0.105N     |
|POLY 6             |     P=0.408N     P=0.212N     P=0.407N     P=0.300N    |P=0.233N     P=0.043N*    P=0.080N     P=0.113N     |
|LOGISTIC REGRESSION|     P=0.399N     P=0.250N     P=0.438N     P=0.310N    |P=0.257N     P=0.033N*    P=0.103N     P=0.104N     |
|COCH-ARM / FISHERS |     P=0.489N     P=0.187N     P=0.349N     P=0.339N    |P=0.261N     P=0.027N*    P=0.102N     P=0.102N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large, Rectum                                                                                                          |
|     Parasite Metazoan                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/47 (0%)    2/49 (4%)    3/49 (6%)    3/49 (6%)   |8/47 (17%)   5/47 (11%)   5/47 (11%)   3/48 (6%)    |
|POLY-3 ADJUSTED (b)|     0.0%         6.4%         9.7%         8.2%        |20.8%        14.1%        12.2%        8.0%         |
|TERMINAL (d)       |     0/6 (0%)     0/5 (0%)     1/6 (17%)    1/8 (13%)   |6/22 (27%)   2/18 (11%)   4/30 (13%)   3/20 (15%)   |
|FIRST INCIDENCE    |     ---          469          574          534         |440          534          705          733 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.316      P=0.215      P=0.110      P=0.155     |P=0.139N     P=0.394N     P=0.134N     P=0.119N     |
|POLY 3             |     P=0.274      P=0.232      P=0.112      P=0.144     |P=0.125N     P=0.329N     P=0.231N     P=0.104N     |
|POLY 1.5           |     P=0.252      P=0.238      P=0.118      P=0.137     |P=0.122N     P=0.315N     P=0.248N     P=0.100N     |
|POLY 6             |     P=0.302      P=0.223      P=0.103      P=0.152     |P=0.135N     P=0.348N     P=0.213N     P=0.114N     |
|LOGISTIC REGRESSION|     P=0.189      P=0.270      P=0.121      P=0.100     |P=0.119N     P=0.309N     P=0.232N     P=0.098N     |
|COCH-ARM / FISHERS |     P=0.222      P=0.258      P=0.129      P=0.129     |P=0.121N     P=0.276N     P=0.276N     P=0.093N     |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 12
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small, Duodenum                                                                                                        |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/49 (4%)    0/49 (0%)    2/50 (4%)    0/49 (0%)   |0/49 (0%)    0/50 (0%)    0/48 (0%)    0/48 (0%)    |
|POLY-3 ADJUSTED (b)|     6.0%         0.0%         6.2%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     706          ---          551          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.270N     P=0.382N     P=0.628      P=0.284N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.246N     P=0.257N     P=0.683      P=0.223N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.264N     P=0.248N     P=0.691      P=0.228N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.225N     P=0.273N     P=0.672      P=0.218N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.282N     P=0.310N     P=0.693      P=0.223N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.290N     P=0.247N     P=0.684N     P=0.247N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    4/49 (8%)    3/50 (6%)    3/50 (6%)   |0/50 (0%)    1/50 (2%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         12.4%        9.4%         8.3%        |0.0%         2.7%         0.0%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     1/5 (20%)    1/6 (17%)    1/8 (13%)   |0/23 (0%)    1/19 (5%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     ---          526          512          636         |---          733 (T)      ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.506      P=0.048 *    P=0.100      P=0.142     |P=0.618N     P=0.462      (e)          (e)          |
|POLY 3             |     P=0.446      P=0.053      P=0.107      P=0.132     |P=0.631N     P=0.483      (e)          (e)          |
|POLY 1.5           |     P=0.425      P=0.055      P=0.113      P=0.127     |P=0.625N     P=0.488      (e)          (e)          |
|POLY 6             |     P=0.472      P=0.049 *    P=0.099      P=0.137     |P=0.641N     P=0.477      (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.423      P=0.062      P=0.114      P=0.134     |(e)          P=0.462      (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.394      P=0.056      P=0.121      P=0.121     |P=0.611N     P=0.500      (e)          (e)          |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 13
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    3/50 (6%)    0/50 (0%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     8.9%         9.6%         0.0%         2.8%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/7 (14%)    1/5 (20%)    0/6 (0%)     1/8 (13%)   |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     683          664          ---          733 (T)     |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.192N     P=0.484      P=0.166N     P=0.302N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.206N     P=0.629      P=0.132N     P=0.282N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.220N     P=0.643      P=0.126N     P=0.291N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.190N     P=0.605      P=0.144N     P=0.277N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.179N     P=0.532      P=0.154N     P=0.281N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.239N     P=0.661N     P=0.121N     P=0.309N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Infarct                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    0/50 (0%)    1/50 (2%)   |1/50 (2%)    0/50 (0%)    0/49 (0%)    2/49 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         3.2%         0.0%         2.8%        |2.5%         0.0%         0.0%         5.0%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |1/23 (4%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     ---          389          ---          701         |733 (T)      ---          ---          469          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.492      P=0.500      (e)          P=0.484     |P=0.175      P=0.538N     P=0.428N     P=0.494      |
|POLY 3             |     P=0.498      P=0.489      (e)          P=0.514     |P=0.181      P=0.517N     P=0.484N     P=0.502      |
|POLY 1.5           |     P=0.490      P=0.494      (e)          P=0.509     |P=0.178      P=0.512N     P=0.492N     P=0.497      |
|POLY 6             |     P=0.506      P=0.481      (e)          P=0.519     |P=0.183      P=0.523N     P=0.475N     P=0.503      |
|LOGISTIC REGRESSION|     P=0.380      P=0.710      (e)          P=0.515     |P=0.174      (e)          (e)          P=0.511      |
|COCH-ARM / FISHERS |     P=0.478      P=0.500      (e)          P=0.500     |P=0.171      P=0.500N     P=0.505N     P=0.492      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 14
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    2/50 (4%)    3/50 (6%)    4/50 (8%)   |0/50 (0%)    0/50 (0%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     11.5%        6.4%         9.3%         11.0%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     1/5 (20%)    0/6 (0%)     2/8 (25%)   |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     539          684          480          604         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.562      P=0.477N     P=0.607N     P=0.603N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.504      P=0.387N     P=0.543N     P=0.621N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.476      P=0.364N     P=0.522N     P=0.627N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.537      P=0.429N     P=0.577N     P=0.623N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.506      P=0.388N     P=0.505N     P=0.606N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.433      P=0.339N     P=0.500N     P=0.643N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Nephropathy                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     50/50 (100%) 48/50 (96%)  50/50 (100%) 50/50 (100%)|46/50 (92%)  46/50 (92%)  46/49 (94%)  46/49 (94%)  |
|POLY-3 ADJUSTED (b)|     100.0%       99.6%        100.0%       100.0%      |95.7%        98.6%        95.9%        97.3%        |
|TERMINAL (d)       |     7/7 (100%)   5/5 (100%)   6/6 (100%)   8/8 (100%)  |22/23 (96%)  19/19 (100%) 33/33 (100%) 22/22 (100%) |
|FIRST INCIDENCE    |     379          460          352          490         |390          420          399          407          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.163N     P=0.231      (e)          (e)         |P=0.486      P=0.194      P=0.032N*    P=0.451      |
|POLY 3             |     P=1.000      P=1.000N     (e)          (e)         |P=0.621      P=0.386      P=0.704      P=0.569      |
|POLY 1.5           |     P=0.904      P=0.830N     (e)          (e)         |P=0.513      P=0.394      P=0.626      P=0.476      |
|POLY 6             |     P=1.000      P=1.000N     (e)          (e)         |P=0.693      P=0.439      P=0.755N     P=0.649      |
|LOGISTIC REGRESSION|     P=0.979      P=0.431N     (e)          (e)         |P=0.487      P=0.358      P=0.633N     P=0.440      |
|COCH-ARM / FISHERS |     P=0.390      P=0.247N     (e)          (e)         |P=0.451      P=0.643N     P=0.511      P=0.511      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 15
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Pelvis                                                                                                                   |
|     Inflammation Acute                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    2/50 (4%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     3.0%         3.2%         6.3%         2.8%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     670          389          628          604         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.557N     P=0.737      P=0.412      P=0.736N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.592N     P=0.749      P=0.477      P=0.746N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.608N     P=0.754      P=0.487      P=0.751N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.573N     P=0.738      P=0.462      P=0.742N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.652      P=0.711N     P=0.475      P=0.762     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.632N     P=0.753N     P=0.500      P=0.753N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    4/50 (8%)    3/50 (6%)    4/50 (8%)   |0/50 (0%)    1/50 (2%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     5.8%         12.7%        9.5%         11.0%       |0.0%         2.7%         0.0%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     1/5 (20%)    1/6 (17%)    2/8 (25%)   |0/23 (0%)    1/19 (5%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     539          664          558          604         |---          733 (T)      ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.520      P=0.233      P=0.437      P=0.397     |P=0.618N     P=0.462      (e)          (e)          |
|POLY 3             |     P=0.456      P=0.292      P=0.460      P=0.362     |P=0.631N     P=0.483      (e)          (e)          |
|POLY 1.5           |     P=0.433      P=0.312      P=0.479      P=0.353     |P=0.625N     P=0.488      (e)          (e)          |
|POLY 6             |     P=0.480      P=0.262      P=0.431      P=0.367     |P=0.641N     P=0.477      (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.490      P=0.287      P=0.483      P=0.355     |(e)          P=0.462      (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.398      P=0.339      P=0.500      P=0.339     |P=0.611N     P=0.500      (e)          (e)          |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 16
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Transitional Epithelium                                                                                                  |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     3.0%         0.0%         0.0%         5.5%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     719          ---          ---          604         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.233      P=0.638N     P=0.602N     P=0.513     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.203      P=0.516N     P=0.516N     P=0.528     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.191      P=0.509N     P=0.509N     P=0.517     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.221      P=0.529N     P=0.529N     P=0.541     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.215      P=0.576N     P=0.543N     P=0.527     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.175      P=0.500N     P=0.500N     P=0.500     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Larynx: Epiglottis                                                                                                               |
|     Metaplasia                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/49 (0%)    0/50 (0%)    1/49 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         2.8%        |0.0%         0.0%         0.0%         5.1%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    2/22 (9%)    |
|FIRST INCIDENCE    |     ---          ---          ---          618         |---          ---          ---          733 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.267      (e)          (e)          P=0.524     |P=0.034 *    (e)          (e)          P=0.227      |
|POLY 3             |     P=0.243      (e)          (e)          P=0.511     |P=0.042 *    (e)          (e)          P=0.233      |
|POLY 1.5           |     P=0.236      (e)          (e)          P=0.505     |P=0.041 *    (e)          (e)          P=0.234      |
|POLY 6             |     P=0.252      (e)          (e)          P=0.518     |P=0.041 *    (e)          (e)          P=0.230      |
|LOGISTIC REGRESSION|     P=0.217      (e)          (e)          P=0.480     |(e)          (e)          (e)          P=0.227      |
|COCH-ARM / FISHERS |     P=0.225      (e)          (e)          P=0.495     |P=0.042 *    (e)          (e)          P=0.247      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 17
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Angiectasis                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    1/50 (2%)    0/50 (0%)    1/50 (2%)   |1/50 (2%)    3/50 (6%)    4/50 (8%)    3/49 (6%)    |
|POLY-3 ADJUSTED (b)|     8.8%         3.2%         0.0%         2.8%        |2.5%         8.0%         9.0%         7.5%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |1/23 (4%)    1/19 (5%)    2/33 (6%)    0/22 (0%)    |
|FIRST INCIDENCE    |     648          579          ---          610         |733 (T)      573          701          597          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.380N     P=0.432N     P=0.160N     P=0.339N    |P=0.422      P=0.254      P=0.279      P=0.293      |
|POLY 3             |     P=0.365N     P=0.332N     P=0.134N     P=0.281N    |P=0.446      P=0.283      P=0.211      P=0.304      |
|POLY 1.5           |     P=0.384N     P=0.320N     P=0.126N     P=0.290N    |P=0.436      P=0.288      P=0.198      P=0.300      |
|POLY 6             |     P=0.338N     P=0.354N     P=0.148N     P=0.274N    |P=0.452      P=0.277      P=0.228      P=0.307      |
|LOGISTIC REGRESSION|     P=0.379N     P=0.339N     P=0.149N     P=0.280N    |P=0.429      P=0.292      P=0.229      P=0.297      |
|COCH-ARM / FISHERS |     P=0.409N     P=0.309N     P=0.121N     P=0.309N    |P=0.426      P=0.309      P=0.181      P=0.301      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Basophilic Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     17/50 (34%)  14/50 (28%)  14/50 (28%)  22/50 (44%) |36/50 (72%)  36/50 (72%)  43/50 (86%)  36/49 (73%)  |
|POLY-3 ADJUSTED (b)|     45.5%        39.7%        41.8%        54.1%       |81.9%        83.1%        92.5%        84.9%        |
|TERMINAL (d)       |     5/7 (71%)    2/5 (40%)    6/6 (100%)   7/8 (88%)   |22/23 (96%)  18/19 (95%)  33/33 (100%) 20/22 (91%)  |
|FIRST INCIDENCE    |     476          526          520          490         |421          440          522          592          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.277      P=0.503      P=0.564N     P=0.316     |P=0.546      P=0.194      P=0.227N     P=0.450      |
|POLY 3             |     P=0.122      P=0.389N     P=0.467N     P=0.283     |P=0.501      P=0.563      P=0.073      P=0.460      |
|POLY 1.5           |     P=0.096      P=0.369N     P=0.399N     P=0.252     |P=0.517      P=0.526      P=0.070      P=0.457      |
|POLY 6             |     P=0.154      P=0.414N     P=0.598N     P=0.315     |P=0.487      P=0.625      P=0.078      P=0.477      |
|LOGISTIC REGRESSION|     P=0.167      P=0.429N     P=0.498N     P=0.290     |P=0.416N     P=0.380      P=0.269      P=0.589      |
|COCH-ARM / FISHERS |     P=0.066      P=0.333N     P=0.333N     P=0.206     |P=0.556N     P=0.588N     P=0.070      P=0.525      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 18
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              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)        |     3/50 (6%)    1/50 (2%)    3/50 (6%)    3/50 (6%)   |6/50 (12%)   9/50 (18%)   12/50 (24%)  5/49 (10%)   |
|POLY-3 ADJUSTED (b)|     8.7%         3.2%         9.5%         8.3%        |15.0%        24.0%        27.3%        12.8%        |
|TERMINAL (d)       |     1/7 (14%)    0/5 (0%)     2/6 (33%)    2/8 (25%)   |5/23 (22%)   7/19 (37%)   12/33 (36%)  5/22 (23%)   |
|FIRST INCIDENCE    |     539          469          558          664         |664          440          733 (T)      733 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.569      P=0.377N     P=0.591      P=0.614N    |P=0.218N     P=0.168      P=0.298      P=0.532N     |
|POLY 3             |     P=0.509      P=0.333N     P=0.624      P=0.642N    |P=0.227N     P=0.234      P=0.132      P=0.521N     |
|POLY 1.5           |     P=0.485      P=0.321N     P=0.642      P=0.648N    |P=0.232N     P=0.250      P=0.116      P=0.520N     |
|POLY 6             |     P=0.537      P=0.356N     P=0.594      P=0.643N    |P=0.234N     P=0.211      P=0.149      P=0.533N     |
|LOGISTIC REGRESSION|     P=0.509      P=0.288N     P=0.618      P=0.626N    |P=0.228N     P=0.208      P=0.196      P=0.556N     |
|COCH-ARM / FISHERS |     P=0.449      P=0.309N     P=0.661N     P=0.661N    |P=0.240N     P=0.288      P=0.096      P=0.514N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         5.5%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     1/8 (13%)   |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          534         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.065      (e)          (e)          P=0.262     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.049 *    (e)          (e)          P=0.255     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.045 *    (e)          (e)          P=0.248     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.053      (e)          (e)          P=0.262     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.044 *    (e)          (e)          P=0.231     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.042 *    (e)          (e)          P=0.247     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 19
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                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 Cystic                                                                                                         |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     12/50 (24%)  10/50 (20%)  14/50 (28%)  16/50 (32%) |0/50 (0%)    0/50 (0%)    2/50 (4%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     33.6%        28.8%        40.4%        41.5%       |0.0%         0.0%         4.5%         0.0%         |
|TERMINAL (d)       |     2/7 (29%)    0/5 (0%)     2/6 (33%)    5/8 (63%)   |0/23 (0%)    0/19 (0%)    1/33 (3%)    0/22 (0%)    |
|FIRST INCIDENCE    |     576          469          512          611         |---          ---          680          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.396      P=0.528      P=0.240      P=0.378     |P=0.670N     (e)          P=0.306      (e)          |
|POLY 3             |     P=0.202      P=0.428N     P=0.359      P=0.316     |P=0.643N     (e)          P=0.261      (e)          |
|POLY 1.5           |     P=0.176      P=0.421N     P=0.382      P=0.290     |P=0.649N     (e)          P=0.251      (e)          |
|POLY 6             |     P=0.232      P=0.442N     P=0.331      P=0.342     |P=0.641N     (e)          P=0.272      (e)          |
|LOGISTIC REGRESSION|     P=0.268      P=0.485N     P=0.268      P=0.343     |P=0.656N     (e)          P=0.258      (e)          |
|COCH-ARM / FISHERS |     P=0.139      P=0.405N     P=0.410      P=0.252     |P=0.657N     (e)          P=0.247      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Degeneration Fatty                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     14/50 (28%)  18/50 (36%)  18/50 (36%)  14/50 (28%) |12/50 (24%)  10/50 (20%)  12/50 (24%)  12/49 (24%)  |
|POLY-3 ADJUSTED (b)|     36.1%        47.0%        44.9%        34.0%       |27.8%        24.5%        25.0%        27.7%        |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    1/19 (5%)    1/33 (3%)    0/22 (0%)    |
|FIRST INCIDENCE    |     476          460          496          490         |496          420          522          512          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.188N     P=0.155      P=0.184      P=0.467N    |P=0.482      P=0.530N     P=0.419N     P=0.556      |
|POLY 3             |     P=0.241N     P=0.218      P=0.276      P=0.518N    |P=0.489      P=0.463N     P=0.474N     P=0.593N     |
|POLY 1.5           |     P=0.281N     P=0.231      P=0.266      P=0.545N    |P=0.471      P=0.449N     P=0.520N     P=0.580      |
|POLY 6             |     P=0.206N     P=0.207      P=0.298      P=0.493N    |P=0.499      P=0.487N     P=0.425N     P=0.586N     |
|LOGISTIC REGRESSION|     P=0.512N     P=0.288      P=0.340      P=0.484     |P=0.434      P=0.350N     P=0.412      P=0.587      |
|COCH-ARM / FISHERS |     P=0.352N     P=0.260      P=0.260      P=0.588N    |P=0.447      P=0.405N     P=0.592N     P=0.570      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 20
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Eosinophilic Focus                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     6/50 (12%)   2/50 (4%)    5/50 (10%)   5/50 (10%)  |6/50 (12%)   6/50 (12%)   5/50 (10%)   9/49 (18%)   |
|POLY-3 ADJUSTED (b)|     17.1%        6.4%         15.5%        13.8%       |14.6%        16.3%        11.2%        22.8%        |
|TERMINAL (d)       |     1/7 (14%)    1/5 (20%)    1/6 (17%)    3/8 (38%)   |4/23 (17%)   4/19 (21%)   4/33 (12%)   6/22 (27%)   |
|FIRST INCIDENCE    |     580          692          558          658         |488          688          534          668          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.540N     P=0.246N     P=0.598      P=0.429N    |P=0.159      P=0.503      P=0.308N     P=0.259      |
|POLY 3             |     P=0.563      P=0.169N     P=0.560N     P=0.477N    |P=0.168      P=0.546      P=0.440N     P=0.257      |
|POLY 1.5           |     P=0.529      P=0.152N     P=0.531N     P=0.483N    |P=0.169      P=0.570      P=0.463N     P=0.261      |
|POLY 6             |     P=0.599N     P=0.204N     P=0.606N     P=0.488N    |P=0.162      P=0.516      P=0.415N     P=0.246      |
|LOGISTIC REGRESSION|     P=0.587N     P=0.173N     P=0.552N     P=0.440N    |P=0.174      P=0.559      P=0.500N     P=0.268      |
|COCH-ARM / FISHERS |     P=0.477      P=0.134N     P=0.500N     P=0.500N    |P=0.169      P=0.620N     P=0.500N     P=0.274      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatodiaphragmatic Nodule                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    2/50 (4%)    1/50 (2%)    2/50 (4%)   |4/50 (8%)    7/50 (14%)   5/50 (10%)   3/49 (6%)    |
|POLY-3 ADJUSTED (b)|     11.2%        6.4%         3.2%         5.5%        |9.9%         18.3%        11.2%        7.5%         |
|TERMINAL (d)       |     0/7 (0%)     1/5 (20%)    0/6 (0%)     0/8 (0%)    |3/23 (13%)   4/19 (21%)   2/33 (6%)    1/22 (5%)    |
|FIRST INCIDENCE    |     379          641          590          534         |573          440          620          407          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.353N     P=0.422N     P=0.212N     P=0.314N    |P=0.249N     P=0.188      P=0.607N     P=0.512N     |
|POLY 3             |     P=0.373N     P=0.398N     P=0.216N     P=0.321N    |P=0.245N     P=0.225      P=0.565      P=0.508N     |
|POLY 1.5           |     P=0.398N     P=0.371N     P=0.199N     P=0.327N    |P=0.247N     P=0.235      P=0.539      P=0.510N     |
|POLY 6             |     P=0.344N     P=0.443N     P=0.244N     P=0.320N    |P=0.254N     P=0.213      P=0.596      P=0.514N     |
|LOGISTIC REGRESSION|     P=0.503N     P=0.302N     P=0.135N     P=0.525N    |P=0.249N     P=0.236      P=0.526      P=0.511N     |
|COCH-ARM / FISHERS |     P=0.431N     P=0.339N     P=0.181N     P=0.339N    |P=0.250N     P=0.262      P=0.500      P=0.511N     |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 21
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                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)        |     3/50 (6%)    2/50 (4%)    4/50 (8%)    0/50 (0%)   |7/50 (14%)   11/50 (22%)  9/50 (18%)   8/49 (16%)   |
|POLY-3 ADJUSTED (b)|     8.8%         6.2%         12.3%        0.0%        |17.4%        28.3%        20.1%        20.0%        |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |4/23 (17%)   3/19 (16%)   8/33 (24%)   5/22 (23%)   |
|FIRST INCIDENCE    |     621          460          590          ---         |642          455          399          597          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.085N     P=0.583N     P=0.360      P=0.117N    |P=0.489N     P=0.133      P=0.566N     P=0.464      |
|POLY 3             |     P=0.083N     P=0.529N     P=0.474      P=0.108N    |P=0.483N     P=0.184      P=0.483      P=0.492      |
|POLY 1.5           |     P=0.092N     P=0.516N     P=0.485      P=0.112N    |P=0.487N     P=0.189      P=0.449      P=0.485      |
|POLY 6             |     P=0.075N     P=0.553N     P=0.460      P=0.107N    |P=0.489N     P=0.179      P=0.516      P=0.492      |
|LOGISTIC REGRESSION|     P=0.117N     P=0.488N     P=0.485      P=0.108N    |P=0.477N     P=0.169      P=0.469      P=0.477      |
|COCH-ARM / FISHERS |     P=0.107N     P=0.500N     P=0.500      P=0.121N    |P=0.490N     P=0.218      P=0.393      P=0.483      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    3/50 (6%)    1/50 (2%)   |2/50 (4%)    0/50 (0%)    2/50 (4%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         6.4%         9.3%         2.8%        |4.9%         0.0%         4.5%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |1/23 (4%)    0/19 (0%)    1/33 (3%)    0/22 (0%)    |
|FIRST INCIDENCE    |     ---          614          496          700         |552          ---          686          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.569N     P=0.169      P=0.111      P=0.500     |P=0.294N     P=0.272N     P=0.603N     P=0.245N     |
|POLY 3             |     P=0.575N     P=0.221      P=0.109      P=0.514     |P=0.278N     P=0.259N     P=0.662N     P=0.245N     |
|POLY 1.5           |     P=0.591N     P=0.228      P=0.113      P=0.509     |P=0.283N     P=0.252N     P=0.674N     P=0.244N     |
|POLY 6             |     P=0.560N     P=0.211      P=0.102      P=0.519     |P=0.276N     P=0.269N     P=0.647N     P=0.249N     |
|LOGISTIC REGRESSION|     P=0.593N     P=0.214      P=0.126      P=0.515     |P=0.293N     P=0.231N     P=0.691      P=0.238N     |
|COCH-ARM / FISHERS |     P=0.615N     P=0.247      P=0.121      P=0.500     |P=0.295N     P=0.247N     P=0.691N     P=0.253N     |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 22
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Regeneration                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |1/50 (2%)    1/50 (2%)    2/50 (4%)    3/49 (6%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         5.6%        |2.5%         2.7%         4.5%         7.6%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     2/8 (25%)   |0/23 (0%)    0/19 (0%)    2/33 (6%)    0/22 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          733 (T)     |608          722          733 (T)      630          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.070      (e)          (e)          P=0.262     |P=0.185      P=0.723      P=0.597      P=0.294      |
|POLY 3             |     P=0.047 *    (e)          (e)          P=0.251     |P=0.200      P=0.740      P=0.531      P=0.299      |
|POLY 1.5           |     P=0.045 *    (e)          (e)          P=0.246     |P=0.195      P=0.746      P=0.519      P=0.297      |
|POLY 6             |     P=0.050      (e)          (e)          P=0.254     |P=0.202      P=0.731      P=0.544      P=0.298      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.262     |P=0.189      P=0.757      P=0.514      P=0.300      |
|COCH-ARM / FISHERS |     P=0.042 *    (e)          (e)          P=0.247     |P=0.188      P=0.753N     P=0.500      P=0.301      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Thrombosis                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     5.8%         0.0%         0.0%         0.0%        |2.5%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     590          ---          ---          ---         |720          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.280N     P=0.261N     P=0.280N     P=0.213N    |P=0.549N     P=0.560N     P=0.454N     P=0.515N     |
|POLY 3             |     P=0.273N     P=0.260N     P=0.260N     P=0.227N    |P=0.549N     P=0.517N     P=0.480N     P=0.505N     |
|POLY 1.5           |     P=0.289N     P=0.250N     P=0.249N     P=0.230N    |P=0.548N     P=0.512N     P=0.488N     P=0.505N     |
|POLY 6             |     P=0.250N     P=0.280N     P=0.280N     P=0.227N    |P=0.550N     P=0.524N     P=0.472N     P=0.507N     |
|LOGISTIC REGRESSION|     P=0.322N     P=0.226N     P=0.227N     P=0.267N    |P=0.552N     P=0.529N     P=0.468N     P=0.511N     |
|COCH-ARM / FISHERS |     P=0.308N     P=0.247N     P=0.247N     P=0.247N    |P=0.551N     P=0.500N     P=0.500N     P=0.505N     |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 23
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Bile Duct                                                                                                                 |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     23/50 (46%)  27/50 (54%)  23/50 (46%)  29/50 (58%) |9/50 (18%)   5/50 (10%)   7/50 (14%)   10/49 (20%)  |
|POLY-3 ADJUSTED (b)|     57.0%        67.6%        58.6%        68.4%       |21.5%        13.4%        15.3%        24.7%        |
|TERMINAL (d)       |     6/7 (86%)    5/5 (100%)   2/6 (33%)    5/8 (63%)   |2/23 (9%)    2/19 (11%)   3/33 (9%)    2/22 (9%)    |
|FIRST INCIDENCE    |     467          482          500          525         |552          635          534          630          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.487N     P=0.100      P=0.323      P=0.338     |P=0.229      P=0.313N     P=0.244N     P=0.454      |
|POLY 3             |     P=0.235      P=0.205      P=0.538      P=0.178     |P=0.227      P=0.259N     P=0.318N     P=0.466      |
|POLY 1.5           |     P=0.213      P=0.229      P=0.550      P=0.171     |P=0.222      P=0.236N     P=0.346N     P=0.468      |
|POLY 6             |     P=0.268      P=0.176      P=0.560      P=0.193     |P=0.228      P=0.294N     P=0.290N     P=0.456      |
|LOGISTIC REGRESSION|     P=0.297      P=0.214      P=0.528      P=0.228     |P=0.216      P=0.224N     P=0.448N     P=0.476      |
|COCH-ARM / FISHERS |     P=0.179      P=0.274      P=0.579N     P=0.158     |P=0.212      P=0.194N     P=0.393N     P=0.480      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Centrilobular                                                                                                             |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     10/50 (20%)  9/50 (18%)   10/50 (20%)  15/50 (30%) |4/50 (8%)    4/50 (8%)    5/50 (10%)   9/49 (18%)   |
|POLY-3 ADJUSTED (b)|     26.9%        25.7%        28.6%        38.3%       |9.8%         10.5%        11.1%        20.9%        |
|TERMINAL (d)       |     1/7 (14%)    0/5 (0%)     1/6 (17%)    2/8 (25%)   |0/23 (0%)    1/19 (5%)    2/33 (6%)    0/22 (0%)    |
|FIRST INCIDENCE    |     467          460          453          525         |608          548          607          407          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.234      P=0.526      P=0.462      P=0.271     |P=0.059      P=0.560      P=0.614      P=0.127      |
|POLY 3             |     P=0.111      P=0.564N     P=0.540      P=0.199     |P=0.062      P=0.602      P=0.557      P=0.132      |
|POLY 1.5           |     P=0.100      P=0.537N     P=0.568      P=0.192     |P=0.054      P=0.613      P=0.535      P=0.120      |
|POLY 6             |     P=0.127      P=0.609N     P=0.494      P=0.203     |P=0.069      P=0.585      P=0.580      P=0.142      |
|LOGISTIC REGRESSION|     P=0.082      P=0.464N     P=0.577N     P=0.196     |P=0.044 *    P=0.641N     P=0.477      P=0.120      |
|COCH-ARM / FISHERS |     P=0.082      P=0.500N     P=0.598N     P=0.178     |P=0.045 *    P=0.643N     P=0.500      P=0.109      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 24
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Inflammation Granulomatous                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     9/50 (18%)   3/50 (6%)    1/50 (2%)    5/50 (10%)  |7/50 (14%)   5/50 (10%)   9/50 (18%)   11/50 (22%)  |
|POLY-3 ADJUSTED (b)|     24.6%        9.2%         3.1%         13.2%       |16.9%        13.5%        20.2%        27.3%        |
|TERMINAL (d)       |     1/7 (14%)    0/5 (0%)     0/6 (0%)     0/8 (0%)    |3/23 (13%)   3/19 (16%)   8/33 (24%)   6/22 (27%)   |
|FIRST INCIDENCE    |     379          460          352          525         |488          603          534          650          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.372N     P=0.137N     P=0.027N*    P=0.183N    |P=0.085      P=0.491N     P=0.580N     P=0.199      |
|POLY 3             |     P=0.379N     P=0.080N     P=0.012N*    P=0.162N    |P=0.095      P=0.457N     P=0.454      P=0.190      |
|POLY 1.5           |     P=0.422N     P=0.071N     P=0.010N*    P=0.175N    |P=0.096      P=0.431N     P=0.431      P=0.198      |
|POLY 6             |     P=0.320N     P=0.098N     P=0.017N*    P=0.151N    |P=0.091      P=0.492N     P=0.477      P=0.175      |
|LOGISTIC REGRESSION|     P=0.588N     P=0.052N     P=0.007N**   P=0.243N    |P=0.094      P=0.417N     P=0.417      P=0.207      |
|COCH-ARM / FISHERS |     P=0.477N     P=0.061N     P=0.008N**   P=0.194N    |P=0.097      P=0.380N     P=0.393      P=0.218      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    2/50 (4%)    1/50 (2%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     5.9%         6.4%         3.2%         2.8%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     1/5 (20%)    0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     639          684          700          700         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.331N     P=0.564      P=0.592N     P=0.496N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.371N     P=0.665      P=0.531N     P=0.479N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.387N     P=0.678      P=0.516N     P=0.487N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.352N     P=0.643      P=0.555N     P=0.475N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.338N     P=0.616      P=0.559N     P=0.470N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.410N     P=0.691N     P=0.500N     P=0.500N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 25
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              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)        |     9/50 (18%)   5/50 (10%)   7/50 (14%)   5/50 (10%)  |9/50 (18%)   9/50 (18%)   7/50 (14%)   6/50 (12%)   |
|POLY-3 ADJUSTED (b)|     24.7%        14.9%        21.2%        13.5%       |22.1%        23.9%        15.9%        15.2%        |
|TERMINAL (d)       |     2/7 (29%)    0/5 (0%)     2/6 (33%)    1/8 (13%)   |5/23 (22%)   5/19 (26%)   7/33 (21%)   4/22 (18%)   |
|FIRST INCIDENCE    |     495          389          520          604         |552          621          733 (T)      671          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.182N     P=0.321N     P=0.526N     P=0.152N    |P=0.241N     P=0.439      P=0.165N     P=0.326N     |
|POLY 3             |     P=0.219N     P=0.231N     P=0.473N     P=0.173N    |P=0.238N     P=0.531      P=0.327N     P=0.304N     |
|POLY 1.5           |     P=0.244N     P=0.213N     P=0.435N     P=0.180N    |P=0.236N     P=0.551      P=0.352N     P=0.300N     |
|POLY 6             |     P=0.194N     P=0.269N     P=0.537N     P=0.174N    |P=0.251N     P=0.507      P=0.302N     P=0.320N     |
|LOGISTIC REGRESSION|     P=0.287N     P=0.167N     P=0.416N     P=0.186N    |P=0.229N     P=0.512      P=0.277N     P=0.305N     |
|COCH-ARM / FISHERS |     P=0.282N     P=0.194N     P=0.393N     P=0.194N    |P=0.233N     P=0.602N     P=0.393N     P=0.288N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung: Artery, Mediastinum                                                                                                        |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    2/50 (4%)    1/50 (2%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     5.9%         6.4%         3.2%         2.8%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     1/5 (20%)    0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     639          684          480          700         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.337N     P=0.564      P=0.588N     P=0.496N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.373N     P=0.665      P=0.524N     P=0.479N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.388N     P=0.678      P=0.512N     P=0.487N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.355N     P=0.643      P=0.544N     P=0.475N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.366N     P=0.616      P=0.493N     P=0.470N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.410N     P=0.691N     P=0.500N     P=0.500N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 26
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Galactocele                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/41 (5%)    7/41 (17%)   1/40 (3%)    4/44 (9%)   |2/50 (4%)    2/50 (4%)    1/50 (2%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     6.5%         24.3%        4.1%         12.7%       |4.9%         5.5%         2.2%         5.0%         |
|TERMINAL (d)       |     0/7 (0%)     1/5 (20%)    1/4 (25%)    0/6 (0%)    |0/23 (0%)    2/19 (11%)   0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     650          547          733 (T)      664         |496          733 (T)      399          657          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.508N     P=0.047 *    P=0.621N     P=0.396     |P=0.618      P=0.635      P=0.476N     P=0.686      |
|POLY 3             |     P=0.587N     P=0.055      P=0.577N     P=0.344     |P=0.608      P=0.655      P=0.468N     P=0.684      |
|POLY 1.5           |     P=0.582N     P=0.064      P=0.546N     P=0.356     |P=0.610      P=0.668      P=0.480N     P=0.686      |
|POLY 6             |     P=0.600N     P=0.042 *    P=0.622N     P=0.323     |P=0.603      P=0.637      P=0.456N     P=0.676      |
|LOGISTIC REGRESSION|     P=0.574N     P=0.061      P=0.634N     P=0.324     |P=0.615      P=0.697      P=0.743N     P=0.684N     |
|COCH-ARM / FISHERS |     P=0.580N     P=0.077      P=0.509N     P=0.372     |P=0.613      P=0.691N     P=0.500N     P=0.691N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery: Artery                                                                                                                |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/15 (0%)    1/10 (10%)   0/8 (0%)     1/11 (9%)   |0/8 (0%)     0/10 (0%)    0/12 (0%)    2/7 (29%)    |
|POLY-3 ADJUSTED (b)|     0.0%         12.3%        0.0%         11.1%       |0.0%         0.0%         0.0%         36.1%        |
|TERMINAL (d)       |     0/5 (0%)     0/2 (0%)     0/3 (0%)     0/1 (0%)    |0/2 (0%)     0/3 (0%)     0/5 (0%)     1/2 (50%)    |
|FIRST INCIDENCE    |     ---          692          ---          608         |---          ---          ---          702          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.527      P=0.427      (e)          P=0.523     |P=0.023 *    (e)          (e)          P=0.228      |
|POLY 3             |     P=0.481      P=0.435      (e)          P=0.458     |P=0.009 **   (e)          (e)          P=0.198      |
|POLY 1.5           |     P=0.471      P=0.429      (e)          P=0.450     |P=0.010 *    (e)          (e)          P=0.195      |
|POLY 6             |     P=0.487      P=0.439      (e)          P=0.463     |P=0.008 **   (e)          (e)          P=0.195      |
|LOGISTIC REGRESSION|     P=0.431      P=0.429      (e)          P=0.344     |P=0.008 **   (e)          (e)          P=0.162      |
|COCH-ARM / FISHERS |     P=0.452      P=0.400      (e)          P=0.423     |P=0.016 *    (e)          (e)          P=0.200      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 27
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                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)        |     14/15 (93%)  9/10 (90%)   8/8 (100%)   8/11 (73%)  |8/8 (100%)   10/10 (100%) 12/12 (100%) 6/7 (86%)    |
|POLY-3 ADJUSTED (b)|     97.2%        91.7%        100.0%       79.2%       |100.0%       100.0%       100.0%       85.7%        |
|TERMINAL (d)       |     5/5 (100%)   2/2 (100%)   3/3 (100%)   1/1 (100%)  |2/2 (100%)   3/3 (100%)   5/5 (100%)   1/2 (50%)    |
|FIRST INCIDENCE    |     477          604          555          604         |496          440          522          559          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.313N     P=0.588N     P=0.357N     P=0.349N    |P=0.259N     (e)          (e)          P=0.417N     |
|POLY 3             |     P=0.099N     P=0.653N     P=0.966      P=0.175N    |P=0.168N     (e)          (e)          P=0.473N     |
|POLY 1.5           |     P=0.090N     P=0.655N     P=0.815      P=0.173N    |P=0.168N     (e)          (e)          P=0.473N     |
|POLY 6             |     P=0.142N     P=0.694N     P=1.000      P=0.225N    |P=0.168N     (e)          (e)          P=0.473N     |
|LOGISTIC REGRESSION|     P=0.058N     P=0.588N     P=0.858      P=0.102N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.092N     P=0.650N     P=0.652      P=0.188N    |P=0.169N     (e)          (e)          P=0.467N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose                                                                                                                             |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     14/49 (29%)  11/49 (22%)  16/50 (32%)  9/49 (18%)  |7/50 (14%)   2/50 (4%)    8/50 (16%)   8/49 (16%)   |
|POLY-3 ADJUSTED (b)|     37.4%        32.4%        43.9%        23.5%       |16.6%        5.4%         18.0%        19.3%        |
|TERMINAL (d)       |     1/7 (14%)    0/5 (0%)     3/6 (50%)    0/8 (0%)    |3/23 (13%)   0/19 (0%)    6/33 (18%)   3/22 (14%)   |
|FIRST INCIDENCE    |     477          527          480          525         |421          565          620          5            |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.099N     P=0.567N     P=0.253      P=0.146N    |P=0.197      P=0.123N     P=0.507N     P=0.481      |
|POLY 3             |     P=0.088N     P=0.419N     P=0.366      P=0.133N    |P=0.232      P=0.109N     P=0.549      P=0.489      |
|POLY 1.5           |     P=0.116N     P=0.373N     P=0.402      P=0.145N    |P=0.222      P=0.099N     P=0.530      P=0.490      |
|POLY 6             |     P=0.064N     P=0.504N     P=0.307      P=0.130N    |P=0.236      P=0.123N     P=0.572      P=0.479      |
|LOGISTIC REGRESSION|     P=0.142N     P=0.366N     P=0.407      P=0.178N    |P=0.188      P=0.068N     P=0.472      P=0.515      |
|COCH-ARM / FISHERS |     P=0.169N     P=0.322N     P=0.440      P=0.170N    |P=0.190      P=0.080N     P=0.500      P=0.483      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 28
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose                                                                                                                             |
|     Thrombosis                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/49 (8%)    7/49 (14%)   10/50 (20%)  6/49 (12%)  |2/50 (4%)    3/50 (6%)    2/50 (4%)    3/49 (6%)    |
|POLY-3 ADJUSTED (b)|     11.6%        20.7%        28.3%        16.2%       |5.0%         7.9%         4.5%         7.4%         |
|TERMINAL (d)       |     0/7 (0%)     1/5 (20%)    0/6 (0%)     1/8 (13%)   |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     590          514          496          505         |663          548          607          512          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.436N     P=0.196      P=0.052      P=0.437     |P=0.494      P=0.443      P=0.641N     P=0.483      |
|POLY 3             |     P=0.519N     P=0.241      P=0.068      P=0.411     |P=0.494      P=0.474      P=0.654N     P=0.503      |
|POLY 1.5           |     P=0.548N     P=0.250      P=0.073      P=0.396     |P=0.488      P=0.479      P=0.670N     P=0.496      |
|POLY 6             |     P=0.493N     P=0.220      P=0.064      P=0.421     |P=0.493      P=0.467      P=0.636N     P=0.505      |
|LOGISTIC REGRESSION|     P=0.493      P=0.283      P=0.094      P=0.364     |P=0.480      P=0.512      P=0.658      P=0.509      |
|COCH-ARM / FISHERS |     P=0.559      P=0.262      P=0.080      P=0.370     |P=0.479      P=0.500      P=0.691N     P=0.490      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose: Lateral Wall                                                                                                               |
|     Metaplasia                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/49 (2%)    0/49 (0%)    0/50 (0%)    0/49 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    3/49 (6%)    |
|POLY-3 ADJUSTED (b)|     3.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         7.5%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    2/22 (9%)    |
|FIRST INCIDENCE    |     467          ---          ---          ---         |---          ---          ---          5            |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.540N     P=0.508N     P=0.504N     P=0.496N    |P=0.007 **   (e)          (e)          P=0.117      |
|POLY 3             |     P=0.523N     P=0.519N     P=0.518N     P=0.491N    |P=0.008 **   (e)          (e)          P=0.118      |
|POLY 1.5           |     P=0.535N     P=0.510N     P=0.507N     P=0.494N    |P=0.007 **   (e)          (e)          P=0.118      |
|POLY 6             |     P=0.504N     P=0.534N     P=0.533N     P=0.490N    |P=0.007 **   (e)          (e)          P=0.116      |
|LOGISTIC REGRESSION|     P=0.712N     P=0.403N     P=0.441N     P=0.793N    |P=0.010 *    (e)          (e)          P=0.152      |
|COCH-ARM / FISHERS |     P=0.547N     P=0.500N     P=0.495N     P=0.500N    |P=0.008 **   (e)          (e)          P=0.117      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 29
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                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)        |     3/49 (6%)    0/49 (0%)    0/50 (0%)    0/49 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     8.9%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/7 (14%)    0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     636          ---          ---          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.158N     P=0.175N     P=0.176N     P=0.105N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.154N     P=0.132N     P=0.131N     P=0.108N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.167N     P=0.126N     P=0.123N     P=0.112N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.133N     P=0.147N     P=0.147N     P=0.106N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.166N     P=0.145N     P=0.143N     P=0.106N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.187N     P=0.121N     P=0.117N     P=0.121N    |(e)          (e)          (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)        |     43/49 (88%)  45/49 (92%)  46/50 (92%)  49/49 (100%)|44/50 (88%)  47/50 (94%)  48/50 (96%)  47/49 (96%)  |
|POLY-3 ADJUSTED (b)|     93.0%        94.8%        96.2%        100.0%      |90.8%        99.5%        96.2%        97.9%        |
|TERMINAL (d)       |     7/7 (100%)   5/5 (100%)   6/6 (100%)   8/8 (100%)  |21/23 (91%)  19/19 (100%) 32/33 (97%)  22/22 (100%) |
|FIRST INCIDENCE    |     379          244          352          490         |390          440          399          407          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.338N     P=0.125      P=0.141      P=0.450     |P=0.400      P=0.108      P=0.133N     P=0.301      |
|POLY 3             |     P=0.033 *    P=0.535      P=0.385      P=0.042 *   |P=0.265      P=0.049 *    P=0.240      P=0.128      |
|POLY 1.5           |     P=0.023 *    P=0.449      P=0.366      P=0.024 *   |P=0.197      P=0.055      P=0.192      P=0.096      |
|POLY 6             |     P=0.075      P=0.693      P=0.462      P=0.136     |P=0.336      P=0.059      P=0.294      P=0.174      |
|LOGISTIC REGRESSION|     P=0.026 *    P=0.341      P=0.296      P=0.027 *   |P=0.182      P=0.086      P=0.154      P=0.106      |
|COCH-ARM / FISHERS |     P=0.019 *    P=0.370      P=0.357      P=0.013 *   |P=0.201      P=0.243      P=0.134      P=0.141      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 30
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                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                                                                                                       |
|     Metaplasia                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/49 (8%)    0/49 (0%)    0/50 (0%)    0/49 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     11.9%        0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     2/7 (29%)    0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     636          ---          ---          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.092N     P=0.104N     P=0.097N     P=0.049N*   |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.087N     P=0.069N     P=0.068N     P=0.052N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.098N     P=0.065N     P=0.063N     P=0.055N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.071N     P=0.078N     P=0.078N     P=0.049N*   |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.098N     P=0.087N     P=0.083N     P=0.051N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.117N     P=0.059N     P=0.056N     P=0.059N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |9/50 (18%)   4/50 (8%)    4/50 (8%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|                                                        |21.3%        10.8%        9.0%         5.0%         |
|TERMINAL (d)       |                                                        |3/23 (13%)   2/19 (11%)   3/33 (9%)    1/22 (5%)    |
|FIRST INCIDENCE    |                                                        |552          688          522          407          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.060N     P=0.201N     P=0.059N     P=0.038N*    |
|POLY 3             |                                                        |P=0.051N     P=0.170N     P=0.092N     P=0.029N*    |
|POLY 1.5           |                                                        |P=0.052N     P=0.149N     P=0.100N     P=0.027N*    |
|POLY 6             |                                                        |P=0.053N     P=0.202N     P=0.087N     P=0.034N*    |
|LOGISTIC REGRESSION|                                                        |P=0.057N     P=0.134N     P=0.141N     P=0.025N*    |
|COCH-ARM / FISHERS |                                                        |P=0.057N     P=0.117N     P=0.117N     P=0.026N*    |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 31
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     22/50 (44%)  17/50 (34%)  26/50 (52%)  18/50 (36%) |9/50 (18%)   11/50 (22%)  17/49 (35%)  10/49 (20%)  |
|POLY-3 ADJUSTED (b)|     55.1%        47.7%        65.2%        44.7%       |20.5%        28.8%        38.4%        23.9%        |
|TERMINAL (d)       |     3/7 (43%)    3/5 (60%)    5/6 (83%)    2/8 (25%)   |2/23 (9%)    5/19 (26%)   13/33 (39%)  3/22 (14%)   |
|FIRST INCIDENCE    |     476          514          352          534         |440          534          534          500          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.147N     P=0.561N     P=0.143      P=0.254N    |P=0.492N     P=0.292      P=0.212      P=0.489      |
|POLY 3             |     P=0.174N     P=0.327N     P=0.225      P=0.223N    |P=0.481N     P=0.269      P=0.050      P=0.452      |
|POLY 1.5           |     P=0.227N     P=0.271N     P=0.248      P=0.240N    |P=0.491N     P=0.311      P=0.049 *    P=0.459      |
|POLY 6             |     P=0.120N     P=0.424N     P=0.197      P=0.209N    |P=0.487N     P=0.225      P=0.052      P=0.435      |
|LOGISTIC REGRESSION|     P=0.211N     P=0.275N     P=0.231      P=0.221N    |P=0.503N     P=0.414      P=0.033 *    P=0.505      |
|COCH-ARM / FISHERS |     P=0.320N     P=0.206N     P=0.274      P=0.270N    |P=0.505N     P=0.402      P=0.048 *    P=0.480      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Basophilic Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    1/50 (2%)    2/50 (4%)   |1/50 (2%)    4/50 (8%)    3/49 (6%)    2/49 (4%)    |
|POLY-3 ADJUSTED (b)|     3.0%         3.2%         3.2%         5.5%        |2.5%         10.7%        6.9%         5.1%         |
|TERMINAL (d)       |     1/7 (14%)    0/5 (0%)     1/6 (17%)    1/8 (13%)   |0/23 (0%)    2/19 (11%)   2/33 (6%)    2/22 (9%)    |
|FIRST INCIDENCE    |     733 (T)      706          733 (T)      650         |488          534          706          733 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.450      P=0.660      P=0.735      P=0.554     |P=0.547N     P=0.152      P=0.394      P=0.490      |
|POLY 3             |     P=0.412      P=0.745      P=0.744      P=0.526     |P=0.552N     P=0.154      P=0.328      P=0.486      |
|POLY 1.5           |     P=0.394      P=0.751      P=0.752      P=0.516     |P=0.548N     P=0.161      P=0.316      P=0.487      |
|POLY 6             |     P=0.435      P=0.734      P=0.732      P=0.537     |P=0.564N     P=0.146      P=0.343      P=0.480      |
|LOGISTIC REGRESSION|     P=0.445      P=0.682      P=0.735      P=0.524     |P=0.537N     P=0.187      P=0.273      P=0.496      |
|COCH-ARM / FISHERS |     P=0.368      P=0.753N     P=0.753N     P=0.500     |P=0.540N     P=0.181      P=0.301      P=0.492      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 32
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    3/50 (6%)    4/50 (8%)    3/50 (6%)   |0/50 (0%)    1/50 (2%)    1/49 (2%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     11.8%        9.5%         12.6%        8.1%        |0.0%         2.7%         2.3%         0.0%         |
|TERMINAL (d)       |     1/7 (14%)    1/5 (20%)    1/6 (17%)    0/8 (0%)    |0/23 (0%)    0/19 (0%)    1/33 (3%)    0/22 (0%)    |
|FIRST INCIDENCE    |     666          583          500          534         |---          719          733 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.384N     P=0.652      P=0.523      P=0.461N    |P=0.528N     P=0.450      P=0.572      (e)          |
|POLY 3             |     P=0.408N     P=0.541N     P=0.610      P=0.454N    |P=0.531N     P=0.484      P=0.516      (e)          |
|POLY 1.5           |     P=0.443N     P=0.523N     P=0.626      P=0.472N    |P=0.530N     P=0.488      P=0.508      (e)          |
|POLY 6             |     P=0.363N     P=0.572N     P=0.583      P=0.436N    |P=0.536N     P=0.477      P=0.525      (e)          |
|LOGISTIC REGRESSION|     P=0.406N     P=0.604N     P=0.558      P=0.463N    |P=0.531N     P=0.472      P=0.572      (e)          |
|COCH-ARM / FISHERS |     P=0.491N     P=0.500N     P=0.643N     P=0.500N    |P=0.527N     P=0.500      P=0.495      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Parathyroid Gland                                                                                                                |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     9/49 (18%)   11/50 (22%)  12/49 (24%)  10/47 (21%) |0/48 (0%)    0/48 (0%)    0/49 (0%)    0/48 (0%)    |
|POLY-3 ADJUSTED (b)|     25.9%        33.5%        35.8%        28.2%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/7 (14%)    2/5 (40%)    1/5 (20%)    2/8 (25%)   |0/21 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     539          624          480          647         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.342N     P=0.173      P=0.176      P=0.552     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.492N     P=0.335      P=0.261      P=0.522     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.540N     P=0.372      P=0.284      P=0.498     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.437N     P=0.281      P=0.227      P=0.546     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.404N     P=0.262      P=0.219      P=0.558     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.522      P=0.421      P=0.312      P=0.459     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 33
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                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)        |     5/50 (10%)   5/49 (10%)   3/50 (6%)    6/49 (12%)  |7/50 (14%)   7/49 (14%)   11/50 (22%)  5/49 (10%)   |
|POLY-3 ADJUSTED (b)|     13.9%        15.5%        9.4%         16.5%       |16.4%        18.7%        24.6%        12.2%        |
|TERMINAL (d)       |     1/7 (14%)    2/5 (40%)    0/6 (0%)     2/8 (25%)   |2/23 (9%)    3/18 (17%)   8/33 (24%)   1/22 (5%)    |
|FIRST INCIDENCE    |     379          523          520          604         |440          420          607          512          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.541      P=0.526      P=0.415N     P=0.563     |P=0.264N     P=0.500      P=0.427      P=0.385N     |
|POLY 3             |     P=0.438      P=0.565      P=0.420N     P=0.508     |P=0.253N     P=0.510      P=0.244      P=0.408N     |
|POLY 1.5           |     P=0.415      P=0.587      P=0.391N     P=0.500     |P=0.261N     P=0.538      P=0.234      P=0.406N     |
|POLY 6             |     P=0.467      P=0.526      P=0.463N     P=0.514     |P=0.252N     P=0.474      P=0.258      P=0.417N     |
|LOGISTIC REGRESSION|     P=0.380      P=0.617N     P=0.315N     P=0.443     |P=0.274N     P=0.574N     P=0.178      P=0.354N     |
|COCH-ARM / FISHERS |     P=0.383      P=0.617      P=0.357N     P=0.486     |P=0.271N     P=0.597      P=0.218      P=0.394N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Preputial Gland                                                                                                                  |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    2/49 (4%)    1/50 (2%)   |                                                    |
|POLY-3 ADJUSTED (b)|     5.8%         3.2%         6.5%         2.8%        |                                                    |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     1/6 (17%)    0/8 (0%)    |                                                    |
|FIRST INCIDENCE    |     539          624          620          667         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.409N     P=0.547N     P=0.615      P=0.473N    |                                                    |
|POLY 3             |     P=0.441N     P=0.534N     P=0.656      P=0.484N    |                                                    |
|POLY 1.5           |     P=0.459N     P=0.519N     P=0.670      P=0.489N    |                                                    |
|POLY 6             |     P=0.421N     P=0.559N     P=0.633      P=0.483N    |                                                    |
|LOGISTIC REGRESSION|     P=0.469N     P=0.482N     P=0.681      P=0.535N    |                                                    |
|COCH-ARM / FISHERS |     P=0.486N     P=0.500N     P=0.684      P=0.500N    |                                                    |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 34
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                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)        |     3/50 (6%)    3/50 (6%)    0/49 (0%)    2/50 (4%)   |                                                    |
|POLY-3 ADJUSTED (b)|     8.7%         9.5%         0.0%         5.5%        |                                                    |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |                                                    |
|FIRST INCIDENCE    |     574          671          ---          667         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.414N     P=0.518      P=0.182N     P=0.493N    |                                                    |
|POLY 3             |     P=0.434N     P=0.622      P=0.139N     P=0.478N    |                                                    |
|POLY 1.5           |     P=0.452N     P=0.639      P=0.131N     P=0.485N    |                                                    |
|POLY 6             |     P=0.412N     P=0.593      P=0.155N     P=0.475N    |                                                    |
|LOGISTIC REGRESSION|     P=0.412N     P=0.616      P=0.129N     P=0.480N    |                                                    |
|COCH-ARM / FISHERS |     P=0.476N     P=0.661N     P=0.125N     P=0.500N    |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Prostate                                                                                                                         |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     6/50 (12%)   6/49 (12%)   6/50 (12%)   7/50 (14%)  |                                                    |
|POLY-3 ADJUSTED (b)|     17.0%        18.6%        18.6%        18.6%       |                                                    |
|TERMINAL (d)       |     2/7 (29%)    2/5 (40%)    2/6 (33%)    3/8 (38%)   |                                                    |
|FIRST INCIDENCE    |     540          583          568          525         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.522N     P=0.461      P=0.507      P=0.566     |                                                    |
|POLY 3             |     P=0.542      P=0.560      P=0.562      P=0.554     |                                                    |
|POLY 1.5           |     P=0.502      P=0.580      P=0.589      P=0.533     |                                                    |
|POLY 6             |     P=0.588N     P=0.527      P=0.523      P=0.573     |                                                    |
|LOGISTIC REGRESSION|     P=0.530      P=0.565      P=0.564      P=0.515     |                                                    |
|COCH-ARM / FISHERS |     P=0.444      P=0.606      P=0.620N     P=0.500     |                                                    |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 35
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Prostate                                                                                                                         |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    4/49 (8%)    4/50 (8%)    6/50 (12%)  |                                                    |
|POLY-3 ADJUSTED (b)|     11.5%        12.5%        12.2%        16.2%       |                                                    |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     1/8 (13%)   |                                                    |
|FIRST INCIDENCE    |     539          537          480          636         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.432      P=0.526      P=0.517      P=0.437     |                                                    |
|POLY 3             |     P=0.339      P=0.603      P=0.613      P=0.409     |                                                    |
|POLY 1.5           |     P=0.315      P=0.616      P=0.627      P=0.394     |                                                    |
|POLY 6             |     P=0.369      P=0.580      P=0.593      P=0.422     |                                                    |
|LOGISTIC REGRESSION|     P=0.314      P=0.616      P=0.641N     P=0.407     |                                                    |
|COCH-ARM / FISHERS |     P=0.279      P=0.631      P=0.643N     P=0.370     |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    1/50 (2%)    5/50 (10%)  |1/50 (2%)    0/50 (0%)    1/50 (2%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     3.0%         0.0%         3.2%         13.6%       |2.5%         0.0%         2.3%         5.1%         |
|TERMINAL (d)       |     1/7 (14%)    0/5 (0%)     0/6 (0%)     2/8 (25%)   |1/23 (4%)    0/19 (0%)    1/33 (3%)    0/22 (0%)    |
|FIRST INCIDENCE    |     733 (T)      ---          680          608         |733 (T)      ---          733 (T)      681          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.021 *    P=0.567N     P=0.709      P=0.139     |P=0.216      P=0.538N     P=0.679N     P=0.471      |
|POLY 3             |     P=0.009 **   P=0.516N     P=0.746      P=0.121     |P=0.249      P=0.517N     P=0.738N     P=0.498      |
|POLY 1.5           |     P=0.007 **   P=0.509N     P=0.753      P=0.113     |P=0.246      P=0.512N     P=0.747N     P=0.497      |
|POLY 6             |     P=0.011 *    P=0.528N     P=0.736      P=0.131     |P=0.251      P=0.523N     P=0.728N     P=0.495      |
|LOGISTIC REGRESSION|     P=0.014 *    (e)          P=0.719      P=0.121     |P=0.232      (e)          P=0.679N     P=0.491      |
|COCH-ARM / FISHERS |     P=0.006 **   P=0.500N     P=0.753N     P=0.102     |P=0.238      P=0.500N     P=0.753N     P=0.500      |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 36
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Fibrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     9/50 (18%)   6/49 (12%)   10/50 (20%)  11/50 (22%) |0/50 (0%)    3/50 (6%)    6/49 (12%)   2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     25.5%        19.0%        30.0%        29.3%       |0.0%         8.2%         13.7%        5.1%         |
|TERMINAL (d)       |     3/7 (43%)    2/5 (40%)    3/6 (50%)    4/8 (50%)   |0/23 (0%)    3/19 (16%)   4/33 (12%)   1/22 (5%)    |
|FIRST INCIDENCE    |     580          660          520          611         |---          733 (T)      607          657          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.442      P=0.505N     P=0.340      P=0.496     |P=0.582      P=0.087      P=0.041 *    P=0.235      |
|POLY 3             |     P=0.317      P=0.361N     P=0.442      P=0.460     |P=0.607      P=0.103      P=0.020 *    P=0.235      |
|POLY 1.5           |     P=0.277      P=0.333N     P=0.469      P=0.438     |P=0.601      P=0.108      P=0.018 *    P=0.235      |
|POLY 6             |     P=0.372      P=0.418N     P=0.400      P=0.479     |P=0.607      P=0.097      P=0.024 *    P=0.233      |
|LOGISTIC REGRESSION|     P=0.383      P=0.416N     P=0.381      P=0.489     |P=0.593      P=0.087      P=0.021 *    P=0.234      |
|COCH-ARM / FISHERS |     P=0.225      P=0.303N     P=0.500      P=0.402     |P=0.592      P=0.121      P=0.012 *    P=0.247      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              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)        |     2/50 (4%)    5/49 (10%)   4/50 (8%)    3/50 (6%)   |5/50 (10%)   2/50 (4%)    3/49 (6%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     5.8%         15.4%        12.1%        8.1%        |11.8%        5.2%         6.9%         4.9%         |
|TERMINAL (d)       |     0/7 (0%)     1/5 (20%)    0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    2/33 (6%)    0/22 (0%)    |
|FIRST INCIDENCE    |     539          469          496          540         |488          216          706          407          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.412N     P=0.170      P=0.297      P=0.546     |P=0.309N     P=0.261N     P=0.273N     P=0.231N     |
|POLY 3             |     P=0.463N     P=0.185      P=0.310      P=0.531     |P=0.297N     P=0.257N     P=0.343N     P=0.231N     |
|POLY 1.5           |     P=0.486N     P=0.195      P=0.322      P=0.519     |P=0.299N     P=0.242N     P=0.352N     P=0.226N     |
|POLY 6             |     P=0.436N     P=0.167      P=0.293      P=0.544     |P=0.300N     P=0.280N     P=0.334N     P=0.244N     |
|LOGISTIC REGRESSION|     P=0.592      P=0.227      P=0.394      P=0.357     |P=0.287N     P=0.095N     P=0.473N     P=0.157N     |
|COCH-ARM / FISHERS |     P=0.521N     P=0.210      P=0.339      P=0.500     |P=0.303N     P=0.218N     P=0.369N     P=0.218N     |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 37
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hemorrhage                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    1/49 (2%)    0/50 (0%)    1/50 (2%)   |1/50 (2%)    0/50 (0%)    0/49 (0%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     2.9%         3.2%         0.0%         2.8%        |2.5%         0.0%         0.0%         4.9%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     590          716          ---          702         |720          ---          ---          469          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.686      P=0.697      P=0.532N     P=0.753     |P=0.180      P=0.560N     P=0.454N     P=0.499      |
|POLY 3             |     P=0.694      P=0.740      P=0.519N     P=0.749N    |P=0.186      P=0.517N     P=0.485N     P=0.507      |
|POLY 1.5           |     P=0.683      P=0.748      P=0.510N     P=0.753N    |P=0.183      P=0.512N     P=0.492N     P=0.503      |
|POLY 6             |     P=0.706      P=0.726      P=0.534N     P=0.748N    |P=0.187      P=0.524N     P=0.476N     P=0.507      |
|LOGISTIC REGRESSION|     P=0.700      P=0.745      P=0.486N     P=0.759N    |P=0.188      P=0.529N     P=0.472N     P=0.550      |
|COCH-ARM / FISHERS |     P=0.669      P=0.747      P=0.500N     P=0.753N    |P=0.176      P=0.500N     P=0.505N     P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/49 (0%)    2/50 (4%)    1/50 (2%)   |1/50 (2%)    0/50 (0%)    0/49 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         6.3%         2.8%        |2.5%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     ---          ---          627          631         |648          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.495      (e)          P=0.186      P=0.532     |P=0.541N     P=0.530N     P=0.474N     P=0.500N     |
|POLY 3             |     P=0.465      (e)          P=0.222      P=0.515     |P=0.544N     P=0.518N     P=0.486N     P=0.504N     |
|POLY 1.5           |     P=0.447      (e)          P=0.229      P=0.509     |P=0.544N     P=0.513N     P=0.493N     P=0.503N     |
|POLY 6             |     P=0.488      (e)          P=0.214      P=0.522     |P=0.543N     P=0.526N     P=0.478N     P=0.509N     |
|LOGISTIC REGRESSION|     P=0.433      (e)          P=0.226      P=0.494     |P=0.546N     P=0.499N     P=0.530N     P=0.498N     |
|COCH-ARM / FISHERS |     P=0.421      (e)          P=0.247      P=0.500     |P=0.546N     P=0.500N     P=0.505N     P=0.500N     |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 38
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                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                                                                                                             |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     17/50 (34%)  16/50 (32%)  19/50 (38%)  10/50 (20%) |7/50 (14%)   7/50 (14%)   6/50 (12%)   5/50 (10%)   |
|POLY-3 ADJUSTED (b)|     42.8%        43.5%        50.2%        26.0%       |16.6%        17.9%        13.0%        12.1%        |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    1/19 (5%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     379          469          480          604         |390          494          399          500          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.033N*    P=0.424      P=0.259      P=0.091N    |P=0.325N     P=0.511      P=0.398N     P=0.400N     |
|POLY 3             |     P=0.032N*    P=0.571      P=0.326      P=0.084N    |P=0.317N     P=0.558      P=0.426N     P=0.387N     |
|POLY 1.5           |     P=0.038N*    P=0.574N     P=0.362      P=0.084N    |P=0.318N     P=0.570      P=0.455N     P=0.388N     |
|POLY 6             |     P=0.031N*    P=0.528      P=0.294      P=0.092N    |P=0.324N     P=0.543      P=0.396N     P=0.393N     |
|LOGISTIC REGRESSION|     P=0.049N*    P=0.497N     P=0.423      P=0.099N    |P=0.312N     P=0.572N     P=0.548      P=0.345N     |
|COCH-ARM / FISHERS |     P=0.053N     P=0.500N     P=0.418      P=0.088N    |P=0.316N     P=0.613N     P=0.500N     P=0.380N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Glandular                                                                                                               |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    3/49 (6%)    5/50 (10%)   4/50 (8%)   |0/50 (0%)    0/50 (0%)    1/50 (2%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     8.7%         9.6%         15.4%        11.0%       |0.0%         0.0%         2.3%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     1/5 (20%)    0/6 (0%)     1/8 (13%)   |0/23 (0%)    0/19 (0%)    1/33 (3%)    0/22 (0%)    |
|FIRST INCIDENCE    |     539          664          480          688         |---          ---          733 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.590      P=0.528      P=0.263      P=0.532     |P=0.786N     (e)          P=0.572      (e)          |
|POLY 3             |     P=0.534      P=0.618      P=0.318      P=0.528     |P=0.770N     (e)          P=0.520      (e)          |
|POLY 1.5           |     P=0.507      P=0.634      P=0.336      P=0.518     |P=0.772N     (e)          P=0.512      (e)          |
|POLY 6             |     P=0.562      P=0.589      P=0.294      P=0.534     |P=0.770N     (e)          P=0.529      (e)          |
|LOGISTIC REGRESSION|     P=0.553      P=0.613      P=0.337      P=0.542     |(e)          (e)          P=0.572      (e)          |
|COCH-ARM / FISHERS |     P=0.468      P=0.651      P=0.357      P=0.500     |P=0.776N     (e)          P=0.500      (e)          |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 39
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                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)        |     8/50 (16%)   5/49 (10%)   11/50 (22%)  9/50 (18%)  |3/50 (6%)    2/50 (4%)    1/50 (2%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     22.0%        15.1%        31.1%        23.8%       |7.5%         5.4%         2.3%         2.5%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     1/8 (13%)   |0/23 (0%)    1/19 (5%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     516          523          516          604         |663          494          626          630          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.528      P=0.416N     P=0.191      P=0.552     |P=0.291N     P=0.586N     P=0.247N     P=0.324N     |
|POLY 3             |     P=0.425      P=0.328N     P=0.268      P=0.538     |P=0.305N     P=0.534N     P=0.270N     P=0.312N     |
|POLY 1.5           |     P=0.395      P=0.311N     P=0.283      P=0.525     |P=0.305N     P=0.524N     P=0.284N     P=0.314N     |
|POLY 6             |     P=0.459      P=0.365N     P=0.256      P=0.545     |P=0.309N     P=0.549N     P=0.256N     P=0.316N     |
|LOGISTIC REGRESSION|     P=0.349      P=0.271N     P=0.311      P=0.531     |P=0.307N     P=0.514N     P=0.301N     P=0.314N     |
|COCH-ARM / FISHERS |     P=0.349      P=0.290N     P=0.306      P=0.500     |P=0.306N     P=0.500N     P=0.309N     P=0.316N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     7/50 (14%)   0/50 (0%)    3/50 (6%)    5/50 (10%)  |                                                    |
|POLY-3 ADJUSTED (b)|     19.5%        0.0%         9.4%         13.5%       |                                                    |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     1/6 (17%)    1/8 (13%)   |                                                    |
|FIRST INCIDENCE    |     552          ---          590          490         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.494      P=0.024N*    P=0.259N     P=0.365N    |                                                    |
|POLY 3             |     P=0.487      P=0.012N*    P=0.202N     P=0.350N    |                                                    |
|POLY 1.5           |     P=0.440      P=0.010N*    P=0.180N     P=0.358N    |                                                    |
|POLY 6             |     P=0.550      P=0.017N*    P=0.246N     P=0.357N    |                                                    |
|LOGISTIC REGRESSION|     P=0.425      P=0.010N*    P=0.175N     P=0.372N    |                                                    |
|COCH-ARM / FISHERS |     P=0.380      P=0.006N**   P=0.159N     P=0.380N    |                                                    |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 40
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    3/50 (6%)    0/50 (0%)    1/50 (2%)   |                                                    |
|POLY-3 ADJUSTED (b)|     0.0%         9.3%         0.0%         2.8%        |                                                    |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     1/8 (13%)   |                                                    |
|FIRST INCIDENCE    |     ---          537          ---          733 (T)     |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.564N     P=0.097      (e)          P=0.527     |                                                    |
|POLY 3             |     P=0.605N     P=0.109      (e)          P=0.513     |                                                    |
|POLY 1.5           |     P=0.614N     P=0.113      (e)          P=0.508     |                                                    |
|POLY 6             |     P=0.595N     P=0.103      (e)          P=0.518     |                                                    |
|LOGISTIC REGRESSION|     P=0.612N     P=0.126      (e)          P=0.527     |                                                    |
|COCH-ARM / FISHERS |     P=0.624N     P=0.121      (e)          P=0.500     |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes: Artery                                                                                                                   |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    2/50 (4%)    1/50 (2%)    3/50 (6%)   |                                                    |
|POLY-3 ADJUSTED (b)|     11.7%        6.3%         3.2%         8.1%        |                                                    |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     1/6 (17%)    0/8 (0%)    |                                                    |
|FIRST INCIDENCE    |     648          583          733 (T)      583         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.536N     P=0.459N     P=0.251N     P=0.467N    |                                                    |
|POLY 3             |     P=0.584N     P=0.372N     P=0.207N     P=0.458N    |                                                    |
|POLY 1.5           |     P=0.612N     P=0.357N     P=0.193N     P=0.474N    |                                                    |
|POLY 6             |     P=0.544N     P=0.401N     P=0.236N     P=0.444N    |                                                    |
|LOGISTIC REGRESSION|     P=0.595N     P=0.382N     P=0.230N     P=0.483N    |                                                    |
|COCH-ARM / FISHERS |     P=0.591      P=0.339N     P=0.181N     P=0.500N    |                                                    |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 41
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes: Interstitial Cell                                                                                                        |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    4/50 (8%)    4/50 (8%)    2/50 (4%)   |                                                    |
|POLY-3 ADJUSTED (b)|     11.5%        12.4%        12.0%        5.5%        |                                                    |
|TERMINAL (d)       |     1/7 (14%)    1/5 (20%)    0/6 (0%)     0/8 (0%)    |                                                    |
|FIRST INCIDENCE    |     560          469          352          607         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.180N     P=0.554      P=0.553      P=0.273N    |                                                    |
|POLY 3             |     P=0.204N     P=0.605      P=0.620      P=0.312N    |                                                    |
|POLY 1.5           |     P=0.223N     P=0.622      P=0.632      P=0.321N    |                                                    |
|POLY 6             |     P=0.185N     P=0.575      P=0.600      P=0.307N    |                                                    |
|LOGISTIC REGRESSION|     P=0.312N     P=0.642      P=0.594N     P=0.356N    |                                                    |
|COCH-ARM / FISHERS |     P=0.250N     P=0.643N     P=0.643N     P=0.339N    |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     32/48 (67%)  36/48 (75%)  34/48 (71%)  26/50 (52%) |37/50 (74%)  34/50 (68%)  38/49 (78%)  35/49 (71%)  |
|POLY-3 ADJUSTED (b)|     73.6%        86.3%        77.1%        59.9%       |77.3%        74.4%        81.1%        79.2%        |
|TERMINAL (d)       |     3/7 (43%)    5/5 (100%)   2/6 (33%)    3/8 (38%)   |17/23 (74%)  12/19 (63%)  27/33 (82%)  17/22 (77%)  |
|FIRST INCIDENCE    |     476          460          352          490         |390          420          399          512          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.027N*    P=0.096      P=0.209      P=0.161N    |P=0.513N     P=0.438      P=0.106N     P=0.523N     |
|POLY 3             |     P=0.007N**   P=0.090      P=0.443      P=0.111N    |P=0.424      P=0.467N     P=0.416      P=0.512      |
|POLY 1.5           |     P=0.008N**   P=0.138      P=0.431      P=0.101N    |P=0.477      P=0.443N     P=0.428      P=0.565      |
|POLY 6             |     P=0.009N**   P=0.052      P=0.470      P=0.141N    |P=0.371      P=0.497N     P=0.391      P=0.454      |
|LOGISTIC REGRESSION|     P=0.015N*    P=0.191      P=0.495      P=0.112N    |P=0.517N     P=0.352N     P=0.449      P=0.492N     |
|COCH-ARM / FISHERS |     P=0.015N*    P=0.250      P=0.413      P=0.102N    |P=0.529N     P=0.330N     P=0.430      P=0.475N     |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 42
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              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)        |     0/48 (0%)    2/48 (4%)    0/48 (0%)    1/50 (2%)   |0/50 (0%)    2/50 (4%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         6.6%         0.0%         2.8%        |0.0%         5.4%         0.0%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    1/19 (5%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     ---          684          ---          631         |---          718          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.689N     P=0.191      (e)          P=0.532     |P=0.393N     P=0.197      (e)          (e)          |
|POLY 3             |     P=0.661      P=0.218      (e)          P=0.520     |P=0.417N     P=0.219      (e)          (e)          |
|POLY 1.5           |     P=0.654      P=0.226      (e)          P=0.515     |P=0.410N     P=0.224      (e)          (e)          |
|POLY 6             |     P=0.668      P=0.207      (e)          P=0.524     |P=0.429N     P=0.212      (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.671      P=0.194      (e)          P=0.502     |P=0.394N     P=0.201      (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.644      P=0.247      (e)          P=0.510     |P=0.394N     P=0.247      (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Tooth                                                                                                                            |
|     Developmental Malformation                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/2 (100%)   1/3 (33%)    0/1 (0%)     1/1 (100%)  |0/0 (0%)     0/0 (0%)     0/1 (0%)     0/0 (0%)     |
|POLY-3 ADJUSTED (b)|     100.0%       46.8%        0.0%         100.0%      |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     |
|FIRST INCIDENCE    |     560          244          ---          702         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.190N     P=0.549N     P=0.324N     (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.791      P=0.448N     P=1.000N     (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.708      P=0.354N     P=1.000N     (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.907      P=0.655N     P=1.000N     (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.648      P=0.172N     (e)          (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.620      P=0.300N     P=0.333N     (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 43
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Tooth                                                                                                                            |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/2 (0%)     2/3 (67%)    1/1 (100%)   0/1 (0%)    |0/0 (0%)     0/0 (0%)     0/1 (0%)     0/0 (0%)     |
|POLY-3 ADJUSTED (b)|     0.0%         98.2%        100.0%       0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     |
|FIRST INCIDENCE    |     ---          537          352          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.358N     P=0.194      P=0.486      (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.424N     P=0.168      P=0.346      (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.559N     P=0.147      P=0.002 **   (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.260N     P=0.561      P=0.889      (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.648N     P=0.172      (e)          (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.620N     P=0.300      P=0.333      (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Trachea                                                                                                                          |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     5.9%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     636          ---          ---          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.274N     P=0.291N     P=0.314N     P=0.217N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.275N     P=0.258N     P=0.258N     P=0.225N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.289N     P=0.249N     P=0.248N     P=0.229N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.252N     P=0.276N     P=0.276N     P=0.224N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.292N     P=0.253N     P=0.253N     P=0.229N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.308N     P=0.247N     P=0.247N     P=0.247N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  06/20/97                           EXPERIMENT: 88070 TEST: 03                                            Page 44
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                ISOBUTENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              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)        |     0/50 (0%)    1/49 (2%)    3/50 (6%)    2/50 (4%)   |0/50 (0%)    0/49 (0%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         3.2%         9.3%         5.5%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     ---          604          480          604         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.419      P=0.488      P=0.098      P=0.288     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.368      P=0.486      P=0.110      P=0.256     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.346      P=0.490      P=0.114      P=0.248     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.396      P=0.478      P=0.104      P=0.265     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.272      P=0.503      P=0.133      P=0.223     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.316      P=0.495      P=0.121      P=0.247     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      500 PPM      2000 PPM     8000 PPM    |CONTROL      500 PPM      2000 PPM     8000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Urinary Bladder: Transitional Epithelium                                                                                         |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    1/49 (2%)    1/50 (2%)    3/50 (6%)   |0/50 (0%)    0/49 (0%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     3.0%         3.2%         3.2%         8.2%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/7 (0%)     0/5 (0%)     0/6 (0%)     0/8 (0%)    |0/23 (0%)    0/19 (0%)    0/33 (0%)    0/22 (0%)    |
|FIRST INCIDENCE    |     719          641          614          604         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.239      P=0.670      P=0.680      P=0.337     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.192      P=0.745      P=0.747      P=0.336     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.178      P=0.750      P=0.753      P=0.323     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.212      P=0.737      P=0.738      P=0.352     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.190      P=0.727      P=0.738      P=0.329     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.159      P=0.747      P=0.753N     P=0.309     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|

(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).