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TDMS Study 05135-07 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10
LAB: Battelle Northwest                                         ISOPRENE                                       DATE: 10/02/97

EXPERIMENT: 05135 TEST: 07                                                                                     TIME: 08:57:12
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:
CONT: NO1-ES-25335                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: 61825B
PATHOLOGIST: GRUMBEIN, S.                                                                                      CAS: 78-79-5
                

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                                         ISOPRENE                                       DATE: 10/02/97     
EXPERIMENT: 05135 TEST: 07                                                                                     TIME: 08:57:12     
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:              
CONT: NO1-ES-25335                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: 61825B     
PATHOLOGIST: GRUMBEIN, S.                                                                                      CAS: 78-79-5       



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

Male Rats
------------
Organ                                 Morphology
-----                                 ----------
Adrenal Medulla                        Hyperplasia
Bone                                   Fibrous Osteodystrophy
Bone Marrow                            Necrosis
Kidney: Renal Tubule                   Hyperplasia
Liver                                  Degeneration Cystic
                                       Regeneration
Liver: Bile Duct                       Hyperplasia
Nose                                   Thrombosis
Nose: Olfactory Epithelium             Atrophy
                                       Metaplasia
Parathyroid Gland                      Hyperplasia
Spleen                                 Fibrosis
Testes: Artery                         Inflammation Chronic
Testes: Interstitial Cell              Hyperplasia
===============================================================
Female Rats
------------
Organ                                  Morphology
-----                                  ----------
Adrenal Cortex                         Hyperplasia
Liver: Bile Duct                       Hyperplasia
Lung                                   Inflammation Chronic
Nose                                   Foreign Body
                                       Inflammation
Spleen                                 Hematopoietic Cell Proliferation
Thyroid Gland: C-Cell                  Hyperplasia
===============================================================
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 1
                     Statistical Analysis of Non-neoplastic Lesions in        Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Degeneration Cystic                                                                                                         |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)   |1/50 (2%)    0/50 (0%)    1/50 (2%)    3/50 (6%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         2.7%        |2.4%         0.0%         2.4%         7.3%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    0/15 (0%)    1/15 (7%)   |0/29 (0%)    0/30 (0%)    0/28 (0%)    2/27 (7%)    |
|FIRST INCIDENCE    |     ---          ---          ---          733 (T)     |714          ---          566          490          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.243      (e)          (e)          P=0.464     |P=0.076      P=0.500N     P=0.751      P=0.280      |
|POLY 3             |     P=0.261      (e)          (e)          P=0.503     |P=0.081      P=0.494N     P=0.759      P=0.294      |
|POLY 1.5           |     P=0.259      (e)          (e)          P=0.501     |P=0.083      P=0.496N     P=0.758      P=0.296      |
|POLY 6             |     P=0.260      (e)          (e)          P=0.501     |P=0.079      P=0.492N     P=0.760      P=0.292      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.464     |P=0.102      P=0.493N     P=0.750N     P=0.310      |
|COCH-ARM / FISHERS |     P=0.260      (e)          (e)          P=0.500     |P=0.089      P=0.500N     P=0.753N     P=0.309      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     23/50 (46%)  23/50 (46%)  19/50 (38%)  20/50 (40%) |25/50 (50%)  17/50 (34%)  20/50 (40%)  13/50 (26%)  |
|POLY-3 ADJUSTED (b)|     56.8%        54.7%        46.8%        49.5%       |55.6%        38.4%        47.5%        31.5%        |
|TERMINAL (d)       |     12/18 (67%)  10/16 (63%)  7/15 (47%)   9/15 (60%)  |17/29 (59%)  14/30 (47%)  16/28 (57%)  11/27 (41%)  |
|FIRST INCIDENCE    |     440          455          510          478         |580          670          672          625          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.455N     P=0.439      P=0.453N     P=0.517N    |P=0.062N     P=0.065N     P=0.261N     P=0.025N*    |
|POLY 3             |     P=0.387N     P=0.514N     P=0.239N     P=0.325N    |P=0.047N*    P=0.072N     P=0.290N     P=0.017N*    |
|POLY 1.5           |     P=0.398N     P=0.528N     P=0.240N     P=0.339N    |P=0.042N*    P=0.072N     P=0.260N     P=0.014N*    |
|POLY 6             |     P=0.386N     P=0.518N     P=0.255N     P=0.330N    |P=0.052N     P=0.081N     P=0.337N     P=0.022N*    |
|LOGISTIC REGRESSION|     P=0.362N     P=0.541N     P=0.248N     P=0.313N    |P=0.050N     P=0.050N     P=0.226N     P=0.015N*    |
|COCH-ARM / FISHERS |     P=0.369N     P=0.579N     P=0.272N     P=0.343N    |P=0.033N*    P=0.078N     P=0.211N     P=0.011N*    |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 2
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Hypertrophy                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     8/50 (16%)   11/50 (22%)  4/50 (8%)    4/50 (8%)   |9/50 (18%)   14/50 (28%)  8/50 (16%)   14/50 (28%)  |
|POLY-3 ADJUSTED (b)|     21.5%        28.1%        10.8%        10.6%       |21.2%        31.2%        18.8%        33.7%        |
|TERMINAL (d)       |     5/18 (28%)   4/16 (25%)   2/15 (13%)   2/15 (13%)  |9/29 (31%)   9/30 (30%)   6/28 (21%)   9/27 (33%)   |
|FIRST INCIDENCE    |     652          588          712          581         |734 (T)      638          547          625          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.143N     P=0.249      P=0.267N     P=0.241N    |P=0.138      P=0.199      P=0.533N     P=0.125      |
|POLY 3             |     P=0.098N     P=0.341      P=0.172N     P=0.162N    |P=0.160      P=0.205      P=0.498N     P=0.146      |
|POLY 1.5           |     P=0.107N     P=0.332      P=0.169N     P=0.170N    |P=0.169      P=0.190      P=0.505N     P=0.149      |
|POLY 6             |     P=0.092N     P=0.345      P=0.187N     P=0.163N    |P=0.155      P=0.226      P=0.485N     P=0.149      |
|LOGISTIC REGRESSION|     P=0.103N     P=0.304      P=0.204N     P=0.172N    |P=0.141      P=0.194      P=0.518N     P=0.123      |
|COCH-ARM / FISHERS |     P=0.112N     P=0.306      P=0.178N     P=0.178N    |P=0.200      P=0.171      P=0.500N     P=0.171      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)   |2/50 (4%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         2.7%         0.0%        |4.7%         0.0%         0.0%         2.4%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    0/15 (0%)    0/15 (0%)   |0/29 (0%)    0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     ---          ---          692          ---         |648          ---          ---          490          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.757N     (e)          P=0.475      (e)         |P=0.644      P=0.237N     P=0.259N     P=0.526N     |
|POLY 3             |     P=0.739N     (e)          P=0.502      (e)         |P=0.650      P=0.231N     P=0.243N     P=0.513N     |
|POLY 1.5           |     P=0.741N     (e)          P=0.503      (e)         |P=0.654      P=0.234N     P=0.242N     P=0.510N     |
|POLY 6             |     P=0.740N     (e)          P=0.497      (e)         |P=0.648      P=0.231N     P=0.244N     P=0.516N     |
|LOGISTIC REGRESSION|     P=0.739N     (e)          P=0.498      (e)         |P=0.697      P=0.238N     P=0.239N     P=0.455N     |
|COCH-ARM / FISHERS |     P=0.740N     (e)          P=0.500      (e)         |P=0.662      P=0.247N     P=0.247N     P=0.500N     |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 3
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Vacuolization Cytoplasmic                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    6/50 (12%)   3/50 (6%)    6/50 (12%)  |4/50 (8%)    6/50 (12%)   4/50 (8%)    6/50 (12%)   |
|POLY-3 ADJUSTED (b)|     5.4%         15.7%        8.1%         15.8%       |9.3%         13.5%        9.6%         14.7%        |
|TERMINAL (d)       |     1/18 (6%)    3/16 (19%)   2/15 (13%)   1/15 (7%)   |2/29 (7%)    5/30 (17%)   4/28 (14%)   4/27 (15%)   |
|FIRST INCIDENCE    |     564          602          667          664         |630          587          734 (T)      713          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.217      P=0.126      P=0.461      P=0.128     |P=0.334      P=0.401      P=0.625      P=0.327      |
|POLY 3             |     P=0.231      P=0.138      P=0.499      P=0.136     |P=0.349      P=0.388      P=0.626      P=0.334      |
|POLY 1.5           |     P=0.224      P=0.139      P=0.505      P=0.134     |P=0.362      P=0.382      P=0.630      P=0.344      |
|POLY 6             |     P=0.238      P=0.133      P=0.484      P=0.135     |P=0.337      P=0.391      P=0.620      P=0.323      |
|LOGISTIC REGRESSION|     P=0.229      P=0.139      P=0.499      P=0.136     |P=0.341      P=0.383      P=0.634      P=0.336      |
|COCH-ARM / FISHERS |     P=0.227      P=0.134      P=0.500      P=0.134     |P=0.392      P=0.370      P=0.643N     P=0.370      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     19/50 (38%)  19/50 (38%)  27/50 (54%)  21/50 (42%) |11/50 (22%)  6/50 (12%)   9/50 (18%)   9/50 (18%)   |
|POLY-3 ADJUSTED (b)|     48.5%        46.2%        64.2%        51.5%       |25.1%        13.5%        21.0%        21.7%        |
|TERMINAL (d)       |     11/18 (61%)  6/16 (38%)   11/15 (73%)  10/15 (67%) |3/29 (10%)   3/30 (10%)   5/28 (18%)   6/27 (22%)   |
|FIRST INCIDENCE    |     468          398          454          517         |580          601          427          594          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.486      P=0.461      P=0.046 *    P=0.280     |P=0.466      P=0.148N     P=0.451N     P=0.476N     |
|POLY 3             |     P=0.548N     P=0.507N     P=0.099      P=0.483     |P=0.483      P=0.132N     P=0.422N     P=0.455N     |
|POLY 1.5           |     P=0.560      P=0.528N     P=0.094      P=0.444     |P=0.501      P=0.135N     P=0.417N     P=0.440N     |
|POLY 6             |     P=0.529N     P=0.492N     P=0.104      P=0.517     |P=0.470      P=0.132N     P=0.432N     P=0.472N     |
|LOGISTIC REGRESSION|     P=0.552N     P=0.550N     P=0.076      P=0.443     |P=0.512      P=0.136N     P=0.412N     P=0.437N     |
|COCH-ARM / FISHERS |     P=0.558N     P=0.582N     P=0.080      P=0.419     |P=0.547      P=0.143N     P=0.402N     P=0.402N     |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 4
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Blood Vessel: Aorta                                                                                                              |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/1 (0%)     0/0 (0%)     2/2 (100%)   3/3 (100%)  |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         100.0%       100.0%      |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     1/1 (100%)  |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     |
|FIRST INCIDENCE    |     ---          ---          566          667         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.236      (e)          P=0.227      P=0.222     |(e)          P=0.486      (e)          P=0.356      |
|POLY 3             |     P=1.000N     (e)          P=1.000      P=1.000N    |(e)          P=0.221      (e)          P=0.269      |
|POLY 1.5           |     P=1.000N     (e)          P=1.000N     P=1.000N    |(e)          P=0.173      (e)          P=0.265      |
|POLY 6             |     P=1.000N     (e)          P=1.000N     P=1.000N    |(e)          P=0.371      (e)          P=0.279      |
|LOGISTIC REGRESSION|     P=0.852      (e)          P=0.358      (e)         |(e)          P=0.313      (e)          P=0.271      |
|COCH-ARM / FISHERS |     P=0.423      (e)          P=0.333      P=0.250     |(e)          P=0.167      (e)          P=0.273      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Fibrous Osteodystrophy                                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    6/50 (12%)   7/50 (14%)  |1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     5.4%         2.7%         15.8%        18.3%       |2.4%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/18 (6%)    0/16 (0%)    2/15 (13%)   1/15 (7%)   |0/29 (0%)    0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     539          657          566          611         |727          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.053      P=0.507N     P=0.120      P=0.079     |P=0.677N     P=0.500N     P=0.520N     P=0.527N     |
|POLY 3             |     P=0.046 *    P=0.496N     P=0.136      P=0.081     |P=0.661N     P=0.494N     P=0.504N     P=0.509N     |
|POLY 1.5           |     P=0.045 *    P=0.495N     P=0.138      P=0.079     |P=0.659N     P=0.496N     P=0.504N     P=0.507N     |
|POLY 6             |     P=0.048 *    P=0.504N     P=0.129      P=0.080     |P=0.663N     P=0.492N     P=0.504N     P=0.511N     |
|LOGISTIC REGRESSION|     P=0.047 *    P=0.502N     P=0.137      P=0.082     |P=0.671N     P=0.493N     P=0.503N     P=0.514N     |
|COCH-ARM / FISHERS |     P=0.048 *    P=0.500N     P=0.134      P=0.080     |P=0.657N     P=0.500N     P=0.500N     P=0.500N     |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 5
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone                                                                                                                             |
|     Hyperostosis                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    1/50 (2%)    2/50 (4%)   |6/50 (12%)   8/50 (16%)   11/50 (22%)  8/50 (16%)   |
|POLY-3 ADJUSTED (b)|     0.0%         2.7%         2.7%         5.3%        |13.9%        17.6%        25.8%        18.7%        |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    0/15 (0%)    1/15 (7%)   |4/29 (14%)   2/30 (7%)    7/28 (25%)   3/27 (11%)   |
|FIRST INCIDENCE    |     ---          693          686          588         |657          587          508          490          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.242      P=0.500      P=0.476      P=0.228     |P=0.504      P=0.429      P=0.138      P=0.350      |
|POLY 3             |     P=0.258      P=0.505      P=0.502      P=0.242     |P=0.552      P=0.429      P=0.132      P=0.381      |
|POLY 1.5           |     P=0.254      P=0.505      P=0.503      P=0.239     |P=0.554      P=0.412      P=0.133      P=0.377      |
|POLY 6             |     P=0.259      P=0.502      P=0.497      P=0.242     |P=0.556      P=0.449      P=0.130      P=0.390      |
|LOGISTIC REGRESSION|     P=0.252      P=0.502      P=0.500      P=0.238     |P=0.568      P=0.386      P=0.132      P=0.390      |
|COCH-ARM / FISHERS |     P=0.252      P=0.500      P=0.500      P=0.247     |P=0.579      P=0.387      P=0.143      P=0.387      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone Marrow                                                                                                                      |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/49 (0%)    2/50 (4%)   |0/49 (0%)    0/49 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         5.4%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    0/15 (0%)    1/15 (7%)   |0/29 (0%)    0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          727         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.042 *    (e)          (e)          P=0.208     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.046 *    (e)          (e)          P=0.239     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.045 *    (e)          (e)          P=0.238     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.046 *    (e)          (e)          P=0.237     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.042 *    (e)          (e)          P=0.207     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.047 *    (e)          (e)          P=0.247     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 6
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral Gland                                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |2/47 (4%)    4/48 (8%)    2/46 (4%)    3/48 (6%)    |
|POLY-3 ADJUSTED (b)|                                                        |5.0%         9.5%         5.3%         7.7%         |
|TERMINAL (d)       |                                                        |2/27 (7%)    3/29 (10%)   2/26 (8%)    3/26 (12%)   |
|FIRST INCIDENCE    |                                                        |734 (T)      727          734 (T)      734 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.537      P=0.365      P=0.683      P=0.482      |
|POLY 3             |                                                        |P=0.550      P=0.359      P=0.676      P=0.485      |
|POLY 1.5           |                                                        |P=0.559      P=0.355      P=0.677      P=0.491      |
|POLY 6             |                                                        |P=0.543      P=0.363      P=0.675      P=0.480      |
|LOGISTIC REGRESSION|                                                        |P=0.533      P=0.355      P=0.683      P=0.482      |
|COCH-ARM / FISHERS |                                                        |P=0.581      P=0.349      P=0.683      P=0.510      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Eye                                                                                                                              |
|     Cataract                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/1 (100%)   1/3 (33%)    3/3 (100%)   2/2 (100%)  |5/5 (100%)   3/4 (75%)    3/3 (100%)   4/6 (67%)    |
|POLY-3 ADJUSTED (b)|     100.0%       41.0%        100.0%       100.0%      |100.0%       79.8%        100.0%       67.6%        |
|TERMINAL (d)       |     1/1 (100%)   0/0 (0%)     2/2 (100%)   1/1 (100%)  |3/3 (100%)   1/1 (100%)   2/2 (100%)   3/4 (75%)    |
|FIRST INCIDENCE    |     733 (T)      602          576          618         |629          601          727          709          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.602      P=0.517      (e)          (e)         |P=0.301N     P=0.677N     (e)          P=0.356N     |
|POLY 3             |     P=0.657      P=0.574N     (e)          (e)         |P=0.213N     P=0.569N     (e)          P=0.269N     |
|POLY 1.5           |     P=0.576      P=0.538N     (e)          (e)         |P=0.229N     P=0.508N     (e)          P=0.265N     |
|POLY 6             |     P=0.764      P=0.638N     (e)          (e)         |P=0.190N     P=0.709N     (e)          P=0.279N     |
|LOGISTIC REGRESSION|     P=0.495      P=0.588N     (e)          (e)         |P=0.216N     P=0.527N     (e)          P=0.271N     |
|COCH-ARM / FISHERS |     P=0.484      P=0.500N     (e)          (e)         |P=0.239N     P=0.444N     (e)          P=0.273N     |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 7
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Eye: Retina                                                                                                                      |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/1 (100%)   2/3 (67%)    3/3 (100%)   2/2 (100%)  |5/5 (100%)   2/4 (50%)    3/3 (100%)   4/6 (67%)    |
|POLY-3 ADJUSTED (b)|     100.0%       79.5%        100.0%       100.0%      |100.0%       59.2%        100.0%       67.6%        |
|TERMINAL (d)       |     1/1 (100%)   0/0 (0%)     2/2 (100%)   1/1 (100%)  |3/3 (100%)   1/1 (100%)   2/2 (100%)   3/4 (75%)    |
|FIRST INCIDENCE    |     733 (T)      602          576          618         |629          601          727          709          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.692      P=0.243      (e)          (e)         |P=0.371N     P=0.486N     (e)          P=0.356N     |
|POLY 3             |     P=0.928      P=0.885N     (e)          (e)         |P=0.308N     P=0.221N     (e)          P=0.269N     |
|POLY 1.5           |     P=0.818      P=0.786N     (e)          (e)         |P=0.352N     P=0.173N     (e)          P=0.265N     |
|POLY 6             |     P=0.999      P=0.995N     (e)          (e)         |P=0.246N     P=0.371N     (e)          P=0.279N     |
|LOGISTIC REGRESSION|     P=0.952      (e)          (e)          (e)         |P=0.238N     P=0.313N     (e)          P=0.271N     |
|COCH-ARM / FISHERS |     P=0.719      P=0.750N     (e)          (e)         |P=0.409N     P=0.167N     (e)          P=0.273N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart                                                                                                                            |
|     Cardiomyopathy                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     41/50 (82%)  44/50 (88%)  44/50 (88%)  38/50 (76%) |35/50 (70%)  33/50 (66%)  28/50 (56%)  37/50 (74%)  |
|POLY-3 ADJUSTED (b)|     88.4%        92.7%        91.4%        85.1%       |76.7%        69.8%        63.6%        82.1%        |
|TERMINAL (d)       |     17/18 (94%)  16/16 (100%) 14/15 (93%)  14/15 (93%) |25/29 (86%)  22/30 (73%)  21/28 (75%)  24/27 (89%)  |
|FIRST INCIDENCE    |     235          398          454          517         |454          482          539          432          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.310N     P=0.262      P=0.223      P=0.555N    |P=0.076      P=0.340N     P=0.171N     P=0.260      |
|POLY 3             |     P=0.184N     P=0.331      P=0.432      P=0.433N    |P=0.090      P=0.295N     P=0.118N     P=0.340      |
|POLY 1.5           |     P=0.184N     P=0.314      P=0.364      P=0.436N    |P=0.104      P=0.345N     P=0.120N     P=0.344      |
|POLY 6             |     P=0.163N     P=0.342      P=0.525      P=0.417N    |P=0.082      P=0.241N     P=0.114N     P=0.356      |
|LOGISTIC REGRESSION|     P=0.100N     P=0.331      P=0.311      P=0.300N    |P=0.073      P=0.342N     P=0.117N     P=0.279      |
|COCH-ARM / FISHERS |     P=0.084N     P=0.288      P=0.288      P=0.312N    |P=0.159      P=0.415N     P=0.107N     P=0.412      |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 8
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart: Artery                                                                                                                    |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    2/50 (4%)    4/50 (8%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     2.7%         0.0%         5.3%         10.6%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/18 (6%)    0/16 (0%)    0/15 (0%)    1/15 (7%)   |0/29 (0%)    0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     733 (T)      ---          566          667         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.053      P=0.523N     P=0.473      P=0.154     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.050      P=0.496N     P=0.509      P=0.184     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.049 *    P=0.496N     P=0.508      P=0.180     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.051      P=0.500N     P=0.504      P=0.183     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.051      (e)          P=0.503      P=0.170     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.051      P=0.500N     P=0.500      P=0.181     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart: Atrium                                                                                                                    |
|     Thrombosis                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    3/50 (6%)    3/50 (6%)    5/50 (10%)  |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     10.6%        7.8%         8.0%         13.0%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    1/15 (7%)    0/15 (0%)   |0/29 (0%)    0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     592          602          555          478         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.333      P=0.519N     P=0.555N     P=0.473     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.331      P=0.491N     P=0.500N     P=0.512     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.323      P=0.490N     P=0.494N     P=0.506     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.335      P=0.501N     P=0.520N     P=0.507     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.323      P=0.496N     P=0.496N     P=0.501     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.325      P=0.500N     P=0.500N     P=0.500     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 9
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large, Rectum                                                                                                          |
|     Inflammation Acute                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/47 (0%)    0/49 (0%)    2/46 (4%)    0/50 (0%)   |0/48 (0%)    0/47 (0%)    0/48 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         5.7%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    0/15 (0%)    0/15 (0%)   |0/27 (0%)    0/30 (0%)    0/27 (0%)    0/26 (0%)    |
|FIRST INCIDENCE    |     ---          ---          555          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.547N     (e)          P=0.245      (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.540N     (e)          P=0.241      (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.543N     (e)          P=0.240      (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.541N     (e)          P=0.238      (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.535N     (e)          P=0.218      (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.544N     (e)          P=0.242      (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small, Duodenum                                                                                                        |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/49 (2%)    1/49 (2%)    2/48 (4%)    2/49 (4%)   |0/49 (0%)    0/48 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     2.7%         2.7%         5.6%         5.3%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    0/15 (0%)    0/15 (0%)   |0/29 (0%)    0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     468          702          681          548         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.474      P=0.758      P=0.489      P=0.516     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.483      P=0.759N     P=0.492      P=0.513     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.477      P=0.758N     P=0.496      P=0.509     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.486      P=0.760      P=0.483      P=0.511     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.465      P=0.739      P=0.478      P=0.469     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.469      P=0.753N     P=0.492      P=0.500     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 10
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    3/50 (6%)    0/49 (0%)   |2/49 (4%)    0/50 (0%)    1/50 (2%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         2.7%         8.1%         0.0%        |4.7%         0.0%         2.4%         4.9%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    3/15 (20%)   0/15 (0%)   |1/29 (3%)    0/30 (0%)    1/28 (4%)    1/27 (4%)    |
|FIRST INCIDENCE    |     ---          703          733 (T)      ---         |539          ---          734 (T)      709          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.356N     P=0.473      P=0.087      (e)         |P=0.371      P=0.234N     P=0.511N     P=0.669      |
|POLY 3             |     P=0.331N     P=0.505      P=0.118      (e)         |P=0.378      P=0.229N     P=0.506N     P=0.679      |
|POLY 1.5           |     P=0.336N     P=0.504      P=0.121      (e)         |P=0.385      P=0.230N     P=0.503N     P=0.685      |
|POLY 6             |     P=0.332N     P=0.502      P=0.112      (e)         |P=0.373      P=0.230N     P=0.510N     P=0.673      |
|LOGISTIC REGRESSION|     P=0.341N     P=0.499      P=0.087      (e)         |P=0.394      P=0.249N     P=0.487N     P=0.690N     |
|COCH-ARM / FISHERS |     P=0.341N     P=0.500      P=0.121      (e)         |P=0.402      P=0.242N     P=0.492N     P=0.684N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    4/50 (8%)    2/50 (4%)   |1/50 (2%)    0/49 (0%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     5.4%         0.0%         10.7%        5.4%        |2.3%         0.0%         0.0%         2.5%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    3/15 (20%)   2/15 (13%)  |0/29 (0%)    0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     604          ---          566          733 (T)     |596          ---          ---          713          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.593      P=0.237N     P=0.309      P=0.676     |P=0.496      P=0.482N     P=0.510N     P=0.748      |
|POLY 3             |     P=0.605      P=0.236N     P=0.336      P=0.694     |P=0.497      P=0.499N     P=0.506N     P=0.749      |
|POLY 1.5           |     P=0.602      P=0.234N     P=0.342      P=0.693     |P=0.501      P=0.501N     P=0.505N     P=0.752      |
|POLY 6             |     P=0.604      P=0.243N     P=0.318      P=0.685     |P=0.493      P=0.497N     P=0.508N     P=0.746      |
|LOGISTIC REGRESSION|     P=0.610      P=0.241N     P=0.340      P=0.692N    |P=0.527      P=0.530N     P=0.465N     P=0.755N     |
|COCH-ARM / FISHERS |     P=0.607      P=0.247N     P=0.339      P=0.691N    |P=0.512      P=0.505N     P=0.500N     P=0.753N     |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 11
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Infarct                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    2/50 (4%)    0/50 (0%)   |0/50 (0%)    1/49 (2%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     2.7%         2.7%         5.3%         0.0%        |0.0%         2.3%         2.4%         0.0%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    1/15 (7%)    0/15 (0%)   |0/29 (0%)    0/30 (0%)    1/28 (4%)    0/27 (0%)    |
|FIRST INCIDENCE    |     564          693          555          ---         |---          622          734 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.295N     P=0.752N     P=0.491      P=0.475N    |P=0.526N     P=0.514      P=0.493      (e)          |
|POLY 3             |     P=0.294N     P=0.759N     P=0.502      P=0.500N    |P=0.519N     P=0.505      P=0.496      (e)          |
|POLY 1.5           |     P=0.296N     P=0.758N     P=0.505      P=0.501N    |P=0.517N     P=0.502      P=0.496      (e)          |
|POLY 6             |     P=0.295N     P=0.759      P=0.492      P=0.504N    |P=0.522N     P=0.510      P=0.496      (e)          |
|LOGISTIC REGRESSION|     P=0.290N     P=0.758      P=0.485      P=0.489N    |P=0.507N     P=0.474      P=0.493      (e)          |
|COCH-ARM / FISHERS |     P=0.292N     P=0.753N     P=0.500      P=0.500N    |P=0.509N     P=0.495      P=0.500      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    2/50 (4%)    3/50 (6%)   |0/50 (0%)    0/49 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         5.3%         8.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    0/15 (0%)    1/15 (7%)   |0/29 (0%)    0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     ---          ---          566          667         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.077      (e)          P=0.233      P=0.113     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.073      (e)          P=0.242      P=0.121     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.071      (e)          P=0.242      P=0.120     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.073      (e)          P=0.238      P=0.120     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.072      (e)          P=0.232      P=0.119     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.073      (e)          P=0.247      P=0.121     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 12
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Nephropathy                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     50/50 (100%) 50/50 (100%) 50/50 (100%) 49/50 (98%) |46/50 (92%)  47/49 (96%)  48/50 (96%)  47/50 (94%)  |
|POLY-3 ADJUSTED (b)|     100.0%       100.0%       100.0%       100.0%      |95.9%        96.7%        99.1%        98.1%        |
|TERMINAL (d)       |     18/18 (100%) 16/16 (100%) 15/15 (100%) 15/15 (100%)|29/29 (100%) 29/30 (97%)  28/28 (100%) 27/27 (100%) |
|FIRST INCIDENCE    |     235          398          454          222         |482          370          427          415          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.531      (e)          (e)          P=0.451     |P=0.281      P=0.512N     P=0.339      P=0.305      |
|POLY 3             |     P=1.000N     (e)          (e)          P=1.000N    |P=0.535      P=0.646      P=0.323      P=0.481      |
|POLY 1.5           |     P=1.000N     (e)          (e)          P=1.000N    |P=0.551      P=0.525      P=0.266      P=0.437      |
|POLY 6             |     P=1.000N     (e)          (e)          P=1.000N    |P=0.519      P=0.761N     P=0.423      P=0.547      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.408      P=0.422      P=0.191      P=0.253      |
|COCH-ARM / FISHERS |     P=0.260N     (e)          (e)          P=0.500N    |P=0.592N     P=0.349      P=0.339      P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    6/50 (12%)   8/50 (16%)  |4/50 (8%)    0/49 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         5.3%         15.6%        20.8%       |9.4%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/18 (0%)    1/16 (6%)    2/15 (13%)   2/15 (13%)  |4/29 (14%)   0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     ---          702          518          548         |734 (T)      ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.012 *    P=0.222      P=0.018 *    P=0.005 **  |P=0.218N     P=0.058N     P=0.066N     P=0.071N     |
|POLY 3             |     P=0.010 *    P=0.241      P=0.017 *    P=0.004 **  |P=0.210N     P=0.057N     P=0.062N     P=0.066N     |
|POLY 1.5           |     P=0.009 **   P=0.242      P=0.017 *    P=0.004 **  |P=0.206N     P=0.060N     P=0.062N     P=0.065N     |
|POLY 6             |     P=0.010 *    P=0.237      P=0.016 *    P=0.004 **  |P=0.215N     P=0.055N     P=0.062N     P=0.066N     |
|LOGISTIC REGRESSION|     P=0.010 *    P=0.226      P=0.018 *    P=0.005 **  |P=0.218N     (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.010 *    P=0.247      P=0.013 *    P=0.003 **  |P=0.202N     P=0.061N     P=0.059N     P=0.059N     |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 13
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Angiectasis                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    5/50 (10%)   3/50 (6%)   |2/50 (4%)    2/50 (4%)    3/50 (6%)    4/50 (8%)    |
|POLY-3 ADJUSTED (b)|     5.4%         0.0%         13.3%        8.0%        |4.6%         4.6%         7.1%         9.8%         |
|TERMINAL (d)       |     1/18 (6%)    0/16 (0%)    1/15 (7%)    2/15 (13%)  |1/29 (3%)    2/30 (7%)    1/28 (4%)    2/27 (7%)    |
|FIRST INCIDENCE    |     723          ---          667          664         |539          734 (T)      604          625          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.409      P=0.282N     P=0.184      P=0.438     |P=0.239      P=0.683N     P=0.481      P=0.304      |
|POLY 3             |     P=0.436      P=0.232N     P=0.223      P=0.509     |P=0.248      P=0.688N     P=0.490      P=0.314      |
|POLY 1.5           |     P=0.428      P=0.232N     P=0.224      P=0.504     |P=0.256      P=0.689N     P=0.491      P=0.320      |
|POLY 6             |     P=0.441      P=0.236N     P=0.218      P=0.508     |P=0.243      P=0.687N     P=0.490      P=0.309      |
|LOGISTIC REGRESSION|     P=0.435      P=0.260N     P=0.203      P=0.484     |P=0.262      P=0.692      P=0.508      P=0.332      |
|COCH-ARM / FISHERS |     P=0.431      P=0.247N     P=0.218      P=0.500     |P=0.275      P=0.691N     P=0.500      P=0.339      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Basophilic Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     17/50 (34%)  13/50 (26%)  13/50 (26%)  16/50 (32%) |36/50 (72%)  38/50 (76%)  33/50 (66%)  33/50 (66%)  |
|POLY-3 ADJUSTED (b)|     43.0%        33.5%        32.9%        41.0%       |79.6%        81.2%        74.8%        75.5%        |
|TERMINAL (d)       |     11/18 (61%)  7/16 (44%)   5/15 (33%)   10/15 (67%) |24/29 (83%)  27/30 (90%)  24/28 (86%)  22/27 (82%)  |
|FIRST INCIDENCE    |     440          581          454          517         |552          587          510          482          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.345      P=0.358N     P=0.386N     P=0.508     |P=0.526N     P=0.527      P=0.441N     P=0.527N     |
|POLY 3             |     P=0.395      P=0.257N     P=0.236N     P=0.523N    |P=0.377N     P=0.530      P=0.376N     P=0.411N     |
|POLY 1.5           |     P=0.388      P=0.249N     P=0.235N     P=0.520N    |P=0.350N     P=0.478      P=0.368N     P=0.399N     |
|POLY 6             |     P=0.396      P=0.283N     P=0.256N     P=0.550N    |P=0.388N     P=0.584      P=0.410N     P=0.418N     |
|LOGISTIC REGRESSION|     P=0.423      P=0.230N     P=0.243N     P=0.478N    |P=0.458N     P=0.564      P=0.383N     P=0.465N     |
|COCH-ARM / FISHERS |     P=0.416      P=0.257N     P=0.257N     P=0.500N    |P=0.269N     P=0.410      P=0.333N     P=0.333N     |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 14
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Clear Cell Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     6/50 (12%)   9/50 (18%)   7/50 (14%)   8/50 (16%)  |9/50 (18%)   11/50 (22%)  10/50 (20%)  11/50 (22%)  |
|POLY-3 ADJUSTED (b)|     16.4%        23.8%        18.1%        21.3%       |21.1%        24.9%        24.0%        27.1%        |
|TERMINAL (d)       |     6/18 (33%)   7/16 (44%)   3/15 (20%)   6/15 (40%)  |8/29 (28%)   9/30 (30%)   10/28 (36%)  11/27 (41%)  |
|FIRST INCIDENCE    |     733 (T)      670          454          630         |705          670          734 (T)      734 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.414      P=0.192      P=0.409      P=0.245     |P=0.349      P=0.430      P=0.467      P=0.323      |
|POLY 3             |     P=0.494      P=0.302      P=0.541      P=0.402     |P=0.380      P=0.435      P=0.478      P=0.351      |
|POLY 1.5           |     P=0.484      P=0.302      P=0.531      P=0.393     |P=0.401      P=0.422      P=0.481      P=0.364      |
|POLY 6             |     P=0.497      P=0.290      P=0.545      P=0.401     |P=0.359      P=0.446      P=0.474      P=0.336      |
|LOGISTIC REGRESSION|     P=0.499      P=0.200      P=0.497      P=0.318     |P=0.338      P=0.429      P=0.478      P=0.306      |
|COCH-ARM / FISHERS |     P=0.491      P=0.288      P=0.500      P=0.387     |P=0.450      P=0.402      P=0.500      P=0.402      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Degeneration Cystic                                                                                                         |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     9/50 (18%)   9/50 (18%)   14/50 (28%)  17/50 (34%) |0/50 (0%)    1/50 (2%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     23.7%        23.3%        35.3%        43.0%       |0.0%         2.3%         0.0%         2.4%         |
|TERMINAL (d)       |     3/18 (17%)   2/16 (13%)   3/15 (20%)   6/15 (40%)  |0/29 (0%)    1/30 (3%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     600          657          537          611         |---          734 (T)      ---          664          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.051      P=0.526      P=0.135      P=0.048 *   |P=0.472      P=0.507      (e)          P=0.495      |
|POLY 3             |     P=0.038 *    P=0.591N     P=0.187      P=0.053     |P=0.480      P=0.507      (e)          P=0.492      |
|POLY 1.5           |     P=0.036 *    P=0.588N     P=0.186      P=0.051     |P=0.482      P=0.504      (e)          P=0.494      |
|POLY 6             |     P=0.041 *    P=0.609N     P=0.178      P=0.053     |P=0.479      P=0.508      (e)          P=0.491      |
|LOGISTIC REGRESSION|     P=0.040 *    P=0.594N     P=0.171      P=0.053     |P=0.481      P=0.507      (e)          P=0.505      |
|COCH-ARM / FISHERS |     P=0.042 *    P=0.602N     P=0.171      P=0.055     |P=0.489      P=0.500      (e)          P=0.500      |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 15
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Eosinophilic Focus                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    4/50 (8%)    3/50 (6%)    3/50 (6%)   |2/50 (4%)    3/50 (6%)    1/50 (2%)    4/50 (8%)    |
|POLY-3 ADJUSTED (b)|     5.5%         10.5%        8.1%         8.0%        |4.7%         6.8%         2.4%         9.8%         |
|TERMINAL (d)       |     2/18 (11%)   1/16 (6%)    1/15 (7%)    2/15 (13%)  |2/29 (7%)    2/30 (7%)    1/28 (4%)    3/27 (11%)   |
|FIRST INCIDENCE    |     733 (T)      657          683          667         |734 (T)      664          734 (T)      625          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.585      P=0.305      P=0.435      P=0.436     |P=0.205      P=0.522      P=0.512N     P=0.306      |
|POLY 3             |     P=0.624      P=0.352      P=0.507      P=0.509     |P=0.220      P=0.518      P=0.507N     P=0.320      |
|POLY 1.5           |     P=0.616      P=0.349      P=0.509      P=0.504     |P=0.225      P=0.511      P=0.506N     P=0.323      |
|POLY 6             |     P=0.626      P=0.350      P=0.499      P=0.509     |P=0.217      P=0.524      P=0.507N     P=0.318      |
|LOGISTIC REGRESSION|     P=0.623      P=0.330      P=0.470      P=0.478     |P=0.207      P=0.518      P=0.512N     P=0.311      |
|COCH-ARM / FISHERS |     P=0.618      P=0.339      P=0.500      P=0.500     |P=0.237      P=0.500      P=0.500N     P=0.339      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Fatty Change                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     15/50 (30%)  12/50 (24%)  9/50 (18%)   11/50 (22%) |8/50 (16%)   6/50 (12%)   11/50 (22%)  9/50 (18%)   |
|POLY-3 ADJUSTED (b)|     35.4%        28.9%        23.0%        27.2%       |17.8%        13.3%        24.9%        20.6%        |
|TERMINAL (d)       |     1/18 (6%)    2/16 (13%)   2/15 (13%)   0/15 (0%)   |1/29 (3%)    1/30 (3%)    1/28 (4%)    0/27 (0%)    |
|FIRST INCIDENCE    |     440          420          518          581         |482          587          547          415          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.428N     P=0.388N     P=0.175N     P=0.283N    |P=0.397      P=0.361N     P=0.301      P=0.455      |
|POLY 3             |     P=0.426N     P=0.340N     P=0.157N     P=0.283N    |P=0.428      P=0.381N     P=0.286      P=0.474      |
|POLY 1.5           |     P=0.435N     P=0.321N     P=0.132N     P=0.272N    |P=0.434      P=0.383N     P=0.288      P=0.478      |
|POLY 6             |     P=0.411N     P=0.392N     P=0.209N     P=0.309N    |P=0.427      P=0.384N     P=0.289      P=0.473      |
|LOGISTIC REGRESSION|     P=0.394N     P=0.369N     P=0.130N     P=0.246N    |P=0.537      P=0.440N     P=0.331      P=0.588      |
|COCH-ARM / FISHERS |     P=0.410N     P=0.326N     P=0.121N     P=0.247N    |P=0.460      P=0.387N     P=0.306      P=0.500      |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 16
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatodiaphragmatic Nodule                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    1/50 (2%)    4/50 (8%)    4/50 (8%)   |2/50 (4%)    4/50 (8%)    5/50 (10%)   6/50 (12%)   |
|POLY-3 ADJUSTED (b)|     2.7%         2.7%         10.6%        10.4%       |4.7%         9.1%         12.0%        14.3%        |
|TERMINAL (d)       |     0/18 (0%)    1/16 (6%)    1/15 (7%)    1/15 (7%)   |2/29 (7%)    3/30 (10%)   5/28 (18%)   4/27 (15%)   |
|FIRST INCIDENCE    |     604          733 (T)      664          560         |734 (T)      670          734 (T)      482          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.190      P=0.754      P=0.170      P=0.197     |P=0.160      P=0.356      P=0.198      P=0.116      |
|POLY 3             |     P=0.195      P=0.760N     P=0.180      P=0.188     |P=0.189      P=0.354      P=0.207      P=0.127      |
|POLY 1.5           |     P=0.186      P=0.758N     P=0.183      P=0.183     |P=0.191      P=0.348      P=0.208      P=0.128      |
|POLY 6             |     P=0.203      P=0.758      P=0.172      P=0.189     |P=0.187      P=0.361      P=0.206      P=0.128      |
|LOGISTIC REGRESSION|     P=0.182      P=0.759N     P=0.181      P=0.180     |P=0.180      P=0.354      P=0.198      P=0.136      |
|COCH-ARM / FISHERS |     P=0.184      P=0.753N     P=0.181      P=0.181     |P=0.202      P=0.339      P=0.218      P=0.134      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Mixed Cell Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    1/50 (2%)   |4/50 (8%)    10/50 (20%)  10/50 (20%)  5/50 (10%)   |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         2.7%        |9.1%         22.0%        22.8%        12.0%        |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    0/15 (0%)    1/15 (7%)   |1/29 (3%)    5/30 (17%)   6/28 (21%)   2/27 (7%)    |
|FIRST INCIDENCE    |     ---          ---          ---          733 (T)     |552          626          510          432          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.243      (e)          (e)          P=0.464     |P=0.308N     P=0.103      P=0.077      P=0.469      |
|POLY 3             |     P=0.261      (e)          (e)          P=0.503     |P=0.286N     P=0.082      P=0.071      P=0.472      |
|POLY 1.5           |     P=0.259      (e)          (e)          P=0.501     |P=0.272N     P=0.078      P=0.070      P=0.479      |
|POLY 6             |     P=0.260      (e)          (e)          P=0.501     |P=0.301N     P=0.086      P=0.072      P=0.464      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.464     |P=0.220N     P=0.066      P=0.083      P=0.543      |
|COCH-ARM / FISHERS |     P=0.260      (e)          (e)          P=0.500     |P=0.243N     P=0.074      P=0.074      P=0.500      |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 17
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Regeneration                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    2/50 (4%)    6/50 (12%)  |0/50 (0%)    1/50 (2%)    2/50 (4%)    3/50 (6%)    |
|POLY-3 ADJUSTED (b)|     5.5%         0.0%         5.3%         15.3%       |0.0%         2.3%         4.8%         7.2%         |
|TERMINAL (d)       |     2/18 (11%)   0/16 (0%)    0/15 (0%)    1/15 (7%)   |0/29 (0%)    1/30 (3%)    2/28 (7%)    1/27 (4%)    |
|FIRST INCIDENCE    |     733 (T)      ---          510          361         |---          734 (T)      734 (T)      490          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.012 *    P=0.263N     P=0.650      P=0.125     |P=0.124      P=0.507      P=0.230      P=0.117      |
|POLY 3             |     P=0.012 *    P=0.232N     P=0.686N     P=0.151     |P=0.132      P=0.507      P=0.232      P=0.115      |
|POLY 1.5           |     P=0.011 *    P=0.232N     P=0.686N     P=0.142     |P=0.133      P=0.504      P=0.233      P=0.115      |
|POLY 6             |     P=0.013 *    P=0.235N     P=0.694N     P=0.157     |P=0.132      P=0.508      P=0.232      P=0.115      |
|LOGISTIC REGRESSION|     P=0.011 *    (e)          P=0.693N     P=0.134     |P=0.145      P=0.507      P=0.230      P=0.144      |
|COCH-ARM / FISHERS |     P=0.011 *    P=0.247N     P=0.691N     P=0.134     |P=0.140      P=0.500      P=0.247      P=0.121      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Bile Duct                                                                                                                 |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     25/50 (50%)  32/50 (64%)  36/50 (72%)  29/50 (58%) |3/50 (6%)    9/50 (18%)   9/50 (18%)   10/50 (20%)  |
|POLY-3 ADJUSTED (b)|     57.8%        74.2%        79.7%        67.0%       |6.9%         19.9%        20.7%        23.1%        |
|TERMINAL (d)       |     7/18 (39%)   13/16 (81%)  11/15 (73%)  9/15 (60%)  |0/29 (0%)    5/30 (17%)   3/28 (11%)   2/27 (7%)    |
|FIRST INCIDENCE    |     468          455          510          222         |539          601          427          490          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.506N     P=0.129      P=0.042 *    P=0.257     |P=0.152      P=0.083      P=0.066      P=0.039 *    |
|POLY 3             |     P=0.453N     P=0.070      P=0.016 *    P=0.246     |P=0.159      P=0.067      P=0.057      P=0.032 *    |
|POLY 1.5           |     P=0.459N     P=0.093      P=0.018 *    P=0.255     |P=0.160      P=0.064      P=0.057      P=0.031 *    |
|POLY 6             |     P=0.470N     P=0.044 *    P=0.013 *    P=0.216     |P=0.165      P=0.069      P=0.057      P=0.033 *    |
|LOGISTIC REGRESSION|     P=0.454N     P=0.130      P=0.022 *    P=0.273     |P=0.204      P=0.052      P=0.069      P=0.046 *    |
|COCH-ARM / FISHERS |     P=0.437N     P=0.113      P=0.020 *    P=0.274     |P=0.178      P=0.061      P=0.061      P=0.036 *    |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 18
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Centrilobular                                                                                                             |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     7/50 (14%)   11/50 (22%)  10/50 (20%)  9/50 (18%)  |5/50 (10%)   5/50 (10%)   8/50 (16%)   3/50 (6%)    |
|POLY-3 ADJUSTED (b)|     18.4%        26.7%        24.8%        22.1%       |11.4%        10.9%        18.4%        7.3%         |
|TERMINAL (d)       |     2/18 (11%)   0/16 (0%)    1/15 (7%)    0/15 (0%)   |0/29 (0%)    0/30 (0%)    1/28 (4%)    0/27 (0%)    |
|FIRST INCIDENCE    |     592          535          537          361         |580          370          508          630          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.546N     P=0.226      P=0.272      P=0.384     |P=0.246N     P=0.597N     P=0.271      P=0.395N     |
|POLY 3             |     P=0.526N     P=0.266      P=0.338      P=0.446     |P=0.244N     P=0.600N     P=0.270      P=0.389N     |
|POLY 1.5           |     P=0.546N     P=0.249      P=0.327      P=0.422     |P=0.230N     P=0.610N     P=0.269      P=0.380N     |
|POLY 6             |     P=0.517N     P=0.282      P=0.344      P=0.462     |P=0.258N     P=0.595N     P=0.271      P=0.399N     |
|LOGISTIC REGRESSION|     P=0.544N     P=0.217      P=0.297      P=0.393     |P=0.151N     P=0.556      P=0.294      P=0.336N     |
|COCH-ARM / FISHERS |     P=0.557N     P=0.218      P=0.298      P=0.393     |P=0.197N     P=0.630N     P=0.277      P=0.357N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     20/49 (41%)  16/50 (32%)  22/50 (44%)  15/50 (30%) |31/50 (62%)  29/50 (58%)  25/50 (50%)  19/50 (38%)  |
|POLY-3 ADJUSTED (b)|     53.1%        38.8%        52.8%        39.1%       |72.5%        63.4%        54.6%        42.4%        |
|TERMINAL (d)       |     16/18 (89%)  7/16 (44%)   9/15 (60%)   8/15 (53%)  |29/29 (100%) 21/30 (70%)  16/28 (57%)  11/27 (41%)  |
|FIRST INCIDENCE    |     482          398          454          560         |671          587          427          114          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.262N     P=0.374N     P=0.221      P=0.365N    |P=0.038N*    P=0.309N     P=0.183N     P=0.022N*    |
|POLY 3             |     P=0.217N     P=0.136N     P=0.583N     P=0.147N    |P=0.006N**   P=0.229N     P=0.053N     P=0.002N**   |
|POLY 1.5           |     P=0.213N     P=0.171N     P=0.547      P=0.166N    |P=0.008N**   P=0.311N     P=0.095N     P=0.005N**   |
|POLY 6             |     P=0.231N     P=0.104N     P=0.520N     P=0.129N    |P=0.004N**   P=0.133N     P=0.020N*    P<0.001N**   |
|LOGISTIC REGRESSION|     P=0.169N     P=0.225N     P=0.433      P=0.171N    |P=0.020N*    P=0.269N     P=0.172N     P=0.019N*    |
|COCH-ARM / FISHERS |     P=0.179N     P=0.241N     P=0.453      P=0.180N    |P=0.013N*    P=0.419N     P=0.157N     P=0.014N*    |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 19
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    2/50 (4%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         5.3%         5.3%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    0/15 (0%)    0/15 (0%)   |0/29 (0%)    0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     ---          ---          566          667         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.238      (e)          P=0.233      P=0.239     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.229      (e)          P=0.243      P=0.243     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.227      (e)          P=0.245      P=0.241     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.231      (e)          P=0.238      P=0.241     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.227      (e)          P=0.238      P=0.241     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.228      (e)          P=0.253      P=0.253     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung: Alveolar Epithelium                                                                                                        |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     7/49 (14%)   11/50 (22%)  4/50 (8%)    10/50 (20%) |5/50 (10%)   5/50 (10%)   10/50 (20%)  8/50 (16%)   |
|POLY-3 ADJUSTED (b)|     18.6%        28.4%        10.4%        25.7%       |11.7%        11.3%        23.9%        19.3%        |
|TERMINAL (d)       |     3/18 (17%)   5/16 (31%)   1/15 (7%)    5/15 (33%)  |4/29 (14%)   4/30 (13%)   9/28 (32%)   5/27 (19%)   |
|FIRST INCIDENCE    |     547          588          469          478         |684          686          672          594          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.255      P=0.184      P=0.309N     P=0.237     |P=0.280      P=0.603N     P=0.115      P=0.237      |
|POLY 3             |     P=0.290      P=0.226      P=0.243N     P=0.317     |P=0.307      P=0.610N     P=0.117      P=0.253      |
|POLY 1.5           |     P=0.282      P=0.234      P=0.240N     P=0.313     |P=0.316      P=0.618N     P=0.120      P=0.257      |
|POLY 6             |     P=0.290      P=0.207      P=0.260N     P=0.303     |P=0.303      P=0.605N     P=0.115      P=0.252      |
|LOGISTIC REGRESSION|     P=0.284      P=0.225      P=0.249N     P=0.310     |P=0.286      P=0.607N     P=0.118      P=0.242      |
|COCH-ARM / FISHERS |     P=0.289      P=0.232      P=0.251N     P=0.314     |P=0.350      P=0.630N     P=0.131      P=0.277      |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 20
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung: Artery, Mediastinum                                                                                                        |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    2/50 (4%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         5.3%         5.3%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    0/15 (0%)    1/15 (7%)   |0/29 (0%)    0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     ---          ---          566          667         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.227      (e)          P=0.233      P=0.223     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.229      (e)          P=0.243      P=0.242     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.226      (e)          P=0.245      P=0.241     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.229      (e)          P=0.238      P=0.240     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.227      (e)          P=0.238      P=0.238     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.228      (e)          P=0.253      P=0.253     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mandibular                                                                                                           |
|     Infiltration Cellular Plasma Cell                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    2/46 (4%)    0/46 (0%)    0/44 (0%)   |0/45 (0%)    0/47 (0%)    0/49 (0%)    0/46 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         5.7%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    0/15 (0%)    0/13 (0%)   |0/27 (0%)    0/28 (0%)    0/27 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     ---          597          ---          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.464N     P=0.246      (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.478N     P=0.232      (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.481N     P=0.230      (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.478N     P=0.233      (e)          (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.481N     P=0.223      (e)          (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.480N     P=0.232      (e)          (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 21
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Galactocele                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/42 (5%)    4/43 (9%)    2/47 (4%)    3/44 (7%)   |1/50 (2%)    1/50 (2%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     6.4%         12.2%        5.7%         8.7%        |2.4%         2.3%         2.4%         0.0%         |
|TERMINAL (d)       |     2/16 (13%)   0/12 (0%)    1/15 (7%)    1/14 (7%)   |1/29 (3%)    0/30 (0%)    1/28 (4%)    0/27 (0%)    |
|FIRST INCIDENCE    |     733 (T)      604          683          621         |734 (T)      714          734 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.570      P=0.296      P=0.671      P=0.469     |P=0.377N     P=0.757N     P=0.754      P=0.514N     |
|POLY 3             |     P=0.603      P=0.353      P=0.655N     P=0.544     |P=0.368N     P=0.753N     P=0.757      P=0.509N     |
|POLY 1.5           |     P=0.591      P=0.353      P=0.651N     P=0.536     |P=0.364N     P=0.756N     P=0.757      P=0.507N     |
|POLY 6             |     P=0.614      P=0.349      P=0.667N     P=0.548     |P=0.372N     P=0.751N     P=0.757      P=0.511N     |
|LOGISTIC REGRESSION|     P=0.593      P=0.335      P=0.697N     P=0.531     |P=0.373N     P=0.754N     P=0.754      (e)          |
|COCH-ARM / FISHERS |     P=0.575      P=0.349      P=0.648N     P=0.522     |P=0.354N     P=0.753N     P=0.753N     P=0.500N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/42 (0%)    0/43 (0%)    0/47 (0%)    0/44 (0%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |2.3%         0.0%         0.0%         4.9%         |
|TERMINAL (d)       |     0/16 (0%)    0/12 (0%)    0/15 (0%)    0/14 (0%)   |0/29 (0%)    0/30 (0%)    0/28 (0%)    2/27 (7%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |596          ---          ---          734 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.147      P=0.482N     P=0.510N     P=0.478      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.152      P=0.496N     P=0.506N     P=0.480      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.155      P=0.497N     P=0.505N     P=0.486      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.149      P=0.495N     P=0.508N     P=0.474      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.159      P=0.525N     P=0.465N     P=0.493      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.163      P=0.500N     P=0.500N     P=0.500      |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 22
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery: Artery                                                                                                                |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/8 (0%)     0/12 (0%)    1/11 (9%)    2/11 (18%)  |0/9 (0%)     0/10 (0%)    0/8 (0%)     0/11 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         12.2%        20.3%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/2 (0%)     0/4 (0%)     0/3 (0%)     1/3 (33%)   |0/5 (0%)     0/4 (0%)     0/2 (0%)     0/4 (0%)     |
|FIRST INCIDENCE    |     ---          ---          566          667         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.145      (e)          P=0.500      P=0.284     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.187      (e)          P=0.576      P=0.367     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.164      (e)          P=0.570      P=0.340     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.225      (e)          P=0.586      P=0.400     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.123      (e)          P=0.552      P=0.363     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.140      (e)          P=0.579      P=0.322     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery: Fat                                                                                                                   |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     6/8 (75%)    10/12 (83%)  8/11 (73%)   6/11 (55%)  |9/9 (100%)   10/10 (100%) 8/8 (100%)   11/11 (100%) |
|POLY-3 ADJUSTED (b)|     82.2%        90.0%        78.8%        59.5%       |100.0%       100.0%       100.0%       100.0%       |
|TERMINAL (d)       |     2/2 (100%)   4/4 (100%)   2/3 (67%)    2/3 (67%)   |5/5 (100%)   4/4 (100%)   2/2 (100%)   4/4 (100%)   |
|FIRST INCIDENCE    |     454          581          521          680         |539          602          427          482          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.298N     P=0.382      P=0.466      P=0.547N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.093N     P=0.600      P=0.676N     P=0.306N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.112N     P=0.564      P=0.671N     P=0.322N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.073N     P=0.710      P=0.662N     P=0.278N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.097N     P=0.598      P=0.661N     P=0.287N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.137N     P=0.535      P=0.664N     P=0.337N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 23
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose                                                                                                                             |
|     Foreign Body                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    4/50 (8%)    3/49 (6%)    2/50 (4%)   |1/50 (2%)    1/50 (2%)    1/50 (2%)    4/50 (8%)    |
|POLY-3 ADJUSTED (b)|     10.8%        10.5%        8.0%         5.4%        |2.4%         2.3%         2.4%         9.8%         |
|TERMINAL (d)       |     2/18 (11%)   3/16 (19%)   0/15 (0%)    2/15 (13%)  |1/29 (3%)    1/30 (3%)    0/28 (0%)    3/27 (11%)   |
|FIRST INCIDENCE    |     664          535          566          733 (T)     |734 (T)      734 (T)      727          653          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.314N     P=0.600      P=0.528N     P=0.394N    |P=0.046 *    P=0.755N     P=0.745      P=0.160      |
|POLY 3             |     P=0.294N     P=0.633N     P=0.497N     P=0.335N    |P=0.051      P=0.754N     P=0.757      P=0.166      |
|POLY 1.5           |     P=0.296N     P=0.631N     P=0.497N     P=0.337N    |P=0.052      P=0.756N     P=0.757      P=0.169      |
|POLY 6             |     P=0.298N     P=0.647N     P=0.504N     P=0.344N    |P=0.049 *    P=0.752N     P=0.757      P=0.164      |
|LOGISTIC REGRESSION|     P=0.285N     P=0.639N     P=0.505N     P=0.341N    |P=0.046 *    P=0.755N     P=0.760      P=0.162      |
|COCH-ARM / FISHERS |     P=0.288N     P=0.643N     P=0.511N     P=0.339N    |P=0.058      P=0.753N     P=0.753N     P=0.181      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose                                                                                                                             |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     11/50 (22%)  9/50 (18%)   10/49 (20%)  9/50 (18%)  |5/50 (10%)   8/50 (16%)   8/50 (16%)   12/50 (24%)  |
|POLY-3 ADJUSTED (b)|     28.4%        23.0%        25.4%        22.7%       |11.7%        17.8%        18.4%        28.0%        |
|TERMINAL (d)       |     5/18 (28%)   5/16 (31%)   1/15 (7%)    3/15 (20%)  |4/29 (14%)   5/30 (17%)   2/28 (7%)    6/27 (22%)   |
|FIRST INCIDENCE    |     482          535          454          222         |630          602          566          114          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.487N     P=0.464N     P=0.563N     P=0.483N    |P=0.053      P=0.308      P=0.260      P=0.048 *    |
|POLY 3             |     P=0.430N     P=0.386N     P=0.482N     P=0.374N    |P=0.056      P=0.308      P=0.283      P=0.049 *    |
|POLY 1.5           |     P=0.440N     P=0.384N     P=0.489N     P=0.384N    |P=0.060      P=0.295      P=0.275      P=0.050      |
|POLY 6             |     P=0.432N     P=0.408N     P=0.487N     P=0.385N    |P=0.054      P=0.321      P=0.298      P=0.050      |
|LOGISTIC REGRESSION|     P=0.447N     P=0.383N     P=0.512N     P=0.400N    |P=0.071      P=0.285      P=0.273      P=0.057      |
|COCH-ARM / FISHERS |     P=0.443N     P=0.402N     P=0.521N     P=0.402N    |P=0.067      P=0.277      P=0.277      P=0.054      |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 24
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose                                                                                                                             |
|     Thrombosis                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    4/50 (8%)    10/49 (20%)  5/50 (10%)  |2/50 (4%)    2/50 (4%)    3/50 (6%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     5.4%         10.2%        25.7%        12.9%       |4.7%         4.5%         7.2%         2.5%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    4/15 (27%)   0/15 (0%)   |0/29 (0%)    0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     592          535          537          478         |580          693          710          713          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.556      P=0.341      P=0.014 *    P=0.217     |P=0.388N     P=0.681N     P=0.481      P=0.528N     |
|POLY 3             |     P=0.583      P=0.359      P=0.014 *    P=0.230     |P=0.377N     P=0.684N     P=0.487      P=0.520N     |
|POLY 1.5           |     P=0.569      P=0.354      P=0.014 *    P=0.223     |P=0.369N     P=0.688N     P=0.490      P=0.514N     |
|POLY 6             |     P=0.592      P=0.361      P=0.014 *    P=0.233     |P=0.385N     P=0.682N     P=0.486      P=0.525N     |
|LOGISTIC REGRESSION|     P=0.566      P=0.319      P=0.015 *    P=0.217     |P=0.360N     P=0.685      P=0.495      P=0.498N     |
|COCH-ARM / FISHERS |     P=0.562      P=0.339      P=0.013 *    P=0.218     |P=0.348N     P=0.691N     P=0.500      P=0.500N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose: Olfactory Epithelium                                                                                                       |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    8/49 (16%)   2/50 (4%)   |0/50 (0%)    1/50 (2%)    2/50 (4%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     2.7%         0.0%         20.6%        5.3%        |0.0%         2.3%         4.8%         4.9%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    0/15 (0%)    0/15 (0%)   |0/29 (0%)    1/30 (3%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     664          ---          518          621         |---          734 (T)      672          653          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.537N     P=0.507N     P=0.022 *    P=0.510     |P=0.313      P=0.507      P=0.239      P=0.220      |
|POLY 3             |     P=0.522N     P=0.497N     P=0.017 *    P=0.508     |P=0.326      P=0.507      P=0.234      P=0.229      |
|POLY 1.5           |     P=0.535N     P=0.496N     P=0.017 *    P=0.503     |P=0.330      P=0.504      P=0.234      P=0.230      |
|POLY 6             |     P=0.510N     P=0.503N     P=0.018 *    P=0.507     |P=0.324      P=0.508      P=0.235      P=0.228      |
|LOGISTIC REGRESSION|     P=0.537N     P=0.497N     P=0.016 *    P=0.500     |P=0.331      P=0.507      P=0.234      P=0.234      |
|COCH-ARM / FISHERS |     P=0.538N     P=0.500N     P=0.014 *    P=0.500     |P=0.345      P=0.500      P=0.247      P=0.247      |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 25
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose: Olfactory Epithelium                                                                                                       |
|     Metaplasia                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     8/50 (16%)   2/50 (4%)    1/49 (2%)    2/50 (4%)   |1/50 (2%)    2/50 (4%)    1/50 (2%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     20.7%        5.3%         2.7%         5.4%        |2.4%         4.5%         2.4%         2.5%         |
|TERMINAL (d)       |     4/18 (22%)   2/16 (13%)   1/15 (7%)    2/15 (13%)  |1/29 (3%)    0/30 (0%)    0/28 (0%)    1/27 (4%)    |
|FIRST INCIDENCE    |     482          733 (T)      733 (T)      733 (T)     |734 (T)      602          638          734 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.258N     P=0.062N     P=0.026N*    P=0.068N    |P=0.611N     P=0.520      P=0.751      P=0.746      |
|POLY 3             |     P=0.221N     P=0.046N*    P=0.018N*    P=0.047N*   |P=0.603N     P=0.518      P=0.758      P=0.751      |
|POLY 1.5           |     P=0.229N     P=0.044N*    P=0.017N*    P=0.047N*   |P=0.597N     P=0.511      P=0.758      P=0.753      |
|POLY 6             |     P=0.211N     P=0.053N     P=0.021N*    P=0.052N    |P=0.608N     P=0.526      P=0.760      P=0.749      |
|LOGISTIC REGRESSION|     P=0.227N     P=0.045N*    P=0.018N*    P=0.046N*   |P=0.574N     P=0.479      P=0.762      P=0.746      |
|COCH-ARM / FISHERS |     P=0.229N     P=0.046N*    P=0.017N*    P=0.046N*   |P=0.586N     P=0.500      P=0.753N     P=0.753N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose: Respiratory Epithelium                                                                                                     |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    2/49 (4%)    2/50 (4%)   |0/50 (0%)    1/50 (2%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     0.0%         5.3%         5.4%         5.2%        |0.0%         2.3%         0.0%         2.4%         |
|TERMINAL (d)       |     0/18 (0%)    1/16 (6%)    0/15 (0%)    0/15 (0%)   |0/29 (0%)    1/30 (3%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     ---          597          454          222         |---          734 (T)      ---          594          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.440      P=0.233      P=0.227      P=0.222     |P=0.478      P=0.507      (e)          P=0.500      |
|POLY 3             |     P=0.471      P=0.244      P=0.239      P=0.246     |P=0.482      P=0.507      (e)          P=0.493      |
|POLY 1.5           |     P=0.464      P=0.243      P=0.239      P=0.242     |P=0.483      P=0.504      (e)          P=0.494      |
|POLY 6             |     P=0.471      P=0.241      P=0.235      P=0.244     |P=0.481      P=0.508      (e)          P=0.493      |
|LOGISTIC REGRESSION|     P=0.515      P=0.240      P=0.205      P=0.271     |P=0.498      P=0.507      (e)          P=0.542      |
|COCH-ARM / FISHERS |     P=0.456      P=0.247      P=0.242      P=0.247     |P=0.489      P=0.500      (e)          P=0.500      |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 26
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |5/50 (10%)   3/50 (6%)    5/50 (10%)   6/50 (12%)   |
|POLY-3 ADJUSTED (b)|                                                        |11.4%        6.8%         12.0%        14.0%        |
|TERMINAL (d)       |                                                        |2/29 (7%)    3/30 (10%)   4/28 (14%)   2/27 (7%)    |
|FIRST INCIDENCE    |                                                        |539          734 (T)      699          464          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.281      P=0.339N     P=0.609      P=0.457      |
|POLY 3             |                                                        |P=0.314      P=0.357N     P=0.599      P=0.481      |
|POLY 1.5           |                                                        |P=0.316      P=0.356N     P=0.608      P=0.485      |
|POLY 6             |                                                        |P=0.313      P=0.363N     P=0.588      P=0.474      |
|LOGISTIC REGRESSION|                                                        |P=0.348      P=0.369N     P=0.628      P=0.583      |
|COCH-ARM / FISHERS |                                                        |P=0.328      P=0.357N     P=0.630N     P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Inflammation Granulomatous                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |0/50 (0%)    1/50 (2%)    0/50 (0%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|                                                        |0.0%         2.3%         0.0%         4.9%         |
|TERMINAL (d)       |                                                        |0/29 (0%)    1/30 (3%)    0/28 (0%)    2/27 (7%)    |
|FIRST INCIDENCE    |                                                        |---          734 (T)      ---          734 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.135      P=0.507      (e)          P=0.222      |
|POLY 3             |                                                        |P=0.144      P=0.507      (e)          P=0.227      |
|POLY 1.5           |                                                        |P=0.147      P=0.504      (e)          P=0.229      |
|POLY 6             |                                                        |P=0.142      P=0.508      (e)          P=0.224      |
|LOGISTIC REGRESSION|                                                        |(e)          P=0.507      (e)          P=0.222      |
|COCH-ARM / FISHERS |                                                        |P=0.153      P=0.500      (e)          P=0.247      |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 27
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     18/50 (36%)  23/50 (46%)  23/50 (46%)  15/50 (30%) |18/50 (36%)  13/50 (26%)  11/50 (22%)  20/50 (40%)  |
|POLY-3 ADJUSTED (b)|     44.9%        54.5%        55.8%        37.0%       |40.7%        29.0%        25.9%        44.8%        |
|TERMINAL (d)       |     8/18 (44%)   8/16 (50%)   9/15 (60%)   3/15 (20%)  |11/29 (38%)  10/30 (33%)  9/28 (32%)   8/27 (30%)   |
|FIRST INCIDENCE    |     482          559          547          548         |482          601          427          490          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.148N     P=0.185      P=0.145      P=0.433N    |P=0.068      P=0.175N     P=0.121N     P=0.345      |
|POLY 3             |     P=0.072N     P=0.248      P=0.213      P=0.305N    |P=0.098      P=0.169N     P=0.104N     P=0.432      |
|POLY 1.5           |     P=0.084N     P=0.235      P=0.220      P=0.323N    |P=0.091      P=0.178N     P=0.101N     P=0.411      |
|POLY 6             |     P=0.067N     P=0.263      P=0.197      P=0.299N    |P=0.119      P=0.165N     P=0.112N     P=0.472      |
|LOGISTIC REGRESSION|     P=0.085N     P=0.228      P=0.216      P=0.325N    |P=0.077      P=0.166N     P=0.100N     P=0.390      |
|COCH-ARM / FISHERS |     P=0.089N     P=0.208      P=0.208      P=0.335N    |P=0.098      P=0.194N     P=0.093N     P=0.418      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Basophilic Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    4/50 (8%)    1/50 (2%)    3/50 (6%)   |1/50 (2%)    0/50 (0%)    3/50 (6%)    3/50 (6%)    |
|POLY-3 ADJUSTED (b)|     2.7%         10.6%        2.7%         8.0%        |2.3%         0.0%         7.2%         7.4%         |
|TERMINAL (d)       |     1/18 (6%)    3/16 (19%)   1/15 (7%)    2/15 (13%)  |0/29 (0%)    0/30 (0%)    3/28 (11%)   3/27 (11%)   |
|FIRST INCIDENCE    |     733 (T)      682          733 (T)      685         |671          ---          734 (T)      734 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.382      P=0.149      P=0.722      P=0.253     |P=0.181      P=0.489N     P=0.299      P=0.282      |
|POLY 3             |     P=0.432      P=0.184      P=0.760N     P=0.311     |P=0.185      P=0.495N     P=0.296      P=0.286      |
|POLY 1.5           |     P=0.425      P=0.185      P=0.758N     P=0.307     |P=0.192      P=0.496N     P=0.298      P=0.292      |
|POLY 6             |     P=0.436      P=0.178      P=0.757      P=0.308     |P=0.179      P=0.494N     P=0.293      P=0.281      |
|LOGISTIC REGRESSION|     P=0.417      P=0.153      P=0.722      P=0.283     |P=0.182      P=0.507N     P=0.297      P=0.284      |
|COCH-ARM / FISHERS |     P=0.425      P=0.181      P=0.753N     P=0.309     |P=0.210      P=0.500N     P=0.309      P=0.309      |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 28
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    6/50 (12%)   9/50 (18%)   7/50 (14%)  |0/50 (0%)    2/50 (4%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     10.9%        16.0%        23.3%        18.1%       |0.0%         4.5%         0.0%         0.0%         |
|TERMINAL (d)       |     3/18 (17%)   5/16 (31%)   4/15 (27%)   4/15 (27%)  |0/29 (0%)    0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     704          682          521          517         |---          714          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.397      P=0.294      P=0.082      P=0.207     |P=0.490N     P=0.240      (e)          (e)          |
|POLY 3             |     P=0.475      P=0.381      P=0.128      P=0.285     |P=0.465N     P=0.245      (e)          (e)          |
|POLY 1.5           |     P=0.453      P=0.382      P=0.126      P=0.273     |P=0.465N     P=0.242      (e)          (e)          |
|POLY 6             |     P=0.495      P=0.368      P=0.125      P=0.291     |P=0.465N     P=0.247      (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.449      P=0.308      P=0.112      P=0.265     |P=0.480N     P=0.246      (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.443      P=0.370      P=0.117      P=0.262     |P=0.464N     P=0.247      (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Metaplasia Hepatocyte                                                                                                       |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    2/50 (4%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |0.0%         4.6%         0.0%         2.5%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    0/15 (0%)    0/15 (0%)   |0/29 (0%)    2/30 (7%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          734 (T)      ---          713          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.611      P=0.245      (e)          P=0.488      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.620      P=0.244      (e)          P=0.491      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.622      P=0.242      (e)          P=0.493      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.619      P=0.246      (e)          P=0.490      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.610      P=0.245      (e)          P=0.490      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.629      P=0.247      (e)          P=0.500      |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 29
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Parathyroid Gland                                                                                                                |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     5/48 (10%)   6/46 (13%)   8/45 (18%)   13/47 (28%) |0/48 (0%)    0/43 (0%)    1/43 (2%)    0/45 (0%)    |
|POLY-3 ADJUSTED (b)|     13.7%        17.1%        23.7%        35.1%       |0.0%         0.0%         2.7%         0.0%         |
|TERMINAL (d)       |     2/17 (12%)   2/14 (14%)   4/13 (31%)   4/14 (29%)  |0/29 (0%)    0/25 (0%)    1/25 (4%)    0/24 (0%)    |
|FIRST INCIDENCE    |     539          597          566          548         |---          ---          734 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.023 *    P=0.431      P=0.196      P=0.032 *   |P=0.758N     (e)          P=0.470      (e)          |
|POLY 3             |     P=0.019 *    P=0.469      P=0.218      P=0.026 *   |P=0.748N     (e)          P=0.476      (e)          |
|POLY 1.5           |     P=0.017 *    P=0.472      P=0.228      P=0.025 *   |P=0.746N     (e)          P=0.476      (e)          |
|POLY 6             |     P=0.021 *    P=0.459      P=0.197      P=0.027 *   |P=0.751N     (e)          P=0.477      (e)          |
|LOGISTIC REGRESSION|     P=0.019 *    P=0.464      P=0.212      P=0.027 *   |(e)          (e)          P=0.470      (e)          |
|COCH-ARM / FISHERS |     P=0.020 *    P=0.470      P=0.235      P=0.029 *   |P=0.740N     (e)          P=0.473      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     5/50 (10%)   6/50 (12%)   9/50 (18%)   11/49 (22%) |12/50 (24%)  16/50 (32%)  7/50 (14%)   12/50 (24%)  |
|POLY-3 ADJUSTED (b)|     13.0%        15.9%        22.9%        27.8%       |26.2%        36.0%        16.2%        28.0%        |
|TERMINAL (d)       |     1/18 (6%)    4/16 (25%)   4/15 (27%)   1/15 (7%)   |5/29 (17%)   12/30 (40%)  3/28 (11%)   7/27 (26%)   |
|FIRST INCIDENCE    |     454          682          521          478         |398          622          539          415          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.094      P=0.443      P=0.171      P=0.095     |P=0.494      P=0.298      P=0.196N     P=0.523      |
|POLY 3             |     P=0.094      P=0.487      P=0.197      P=0.087     |P=0.534      P=0.217      P=0.185N     P=0.518      |
|POLY 1.5           |     P=0.082      P=0.498      P=0.201      P=0.080     |P=0.549      P=0.231      P=0.177N     P=0.539      |
|POLY 6             |     P=0.111      P=0.461      P=0.187      P=0.094     |P=0.520      P=0.198      P=0.192N     P=0.496      |
|LOGISTIC REGRESSION|     P=0.078      P=0.511      P=0.187      P=0.079     |P=0.553N     P=0.246      P=0.127N     P=0.548N     |
|COCH-ARM / FISHERS |     P=0.079      P=0.500      P=0.194      P=0.079     |P=0.557N     P=0.252      P=0.154N     P=0.592N     |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 30
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Preputial Gland                                                                                                                  |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    1/50 (2%)    3/50 (6%)   |                                                    |
|POLY-3 ADJUSTED (b)|     5.4%         2.7%         2.7%         7.9%        |                                                    |
|TERMINAL (d)       |     1/18 (6%)    0/16 (0%)    0/15 (0%)    0/15 (0%)   |                                                    |
|FIRST INCIDENCE    |     547          702          521          611         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.272      P=0.513N     P=0.510N     P=0.504     |                                                    |
|POLY 3             |     P=0.262      P=0.497N     P=0.497N     P=0.508     |                                                    |
|POLY 1.5           |     P=0.257      P=0.495N     P=0.495N     P=0.503     |                                                    |
|POLY 6             |     P=0.269      P=0.506N     P=0.508N     P=0.509     |                                                    |
|LOGISTIC REGRESSION|     P=0.260      P=0.496N     P=0.528N     P=0.500     |                                                    |
|COCH-ARM / FISHERS |     P=0.258      P=0.500N     P=0.500N     P=0.500     |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Prostate                                                                                                                         |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     11/50 (22%)  13/50 (26%)  15/50 (30%)  17/50 (34%) |                                                    |
|POLY-3 ADJUSTED (b)|     29.4%        34.3%        38.7%        42.3%       |                                                    |
|TERMINAL (d)       |     7/18 (39%)   9/16 (56%)   8/15 (53%)   8/15 (53%)  |                                                    |
|FIRST INCIDENCE    |     659          682          454          560         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.116      P=0.281      P=0.140      P=0.088     |                                                    |
|POLY 3             |     P=0.203      P=0.413      P=0.263      P=0.165     |                                                    |
|POLY 1.5           |     P=0.171      P=0.422      P=0.267      P=0.145     |                                                    |
|POLY 6             |     P=0.252      P=0.375      P=0.235      P=0.184     |                                                    |
|LOGISTIC REGRESSION|     P=0.158      P=0.337      P=0.213      P=0.132     |                                                    |
|COCH-ARM / FISHERS |     P=0.161      P=0.408      P=0.247      P=0.133     |                                                    |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 31
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Prostate                                                                                                                         |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     5/50 (10%)   2/50 (4%)    1/50 (2%)    6/50 (12%)  |                                                    |
|POLY-3 ADJUSTED (b)|     13.3%        5.3%         2.7%         15.6%       |                                                    |
|TERMINAL (d)       |     3/18 (17%)   1/16 (6%)    1/15 (7%)    3/15 (20%)  |                                                    |
|FIRST INCIDENCE    |     235          702          733 (T)      566         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.105      P=0.265N     P=0.144N     P=0.437     |                                                    |
|POLY 3             |     P=0.126      P=0.214N     P=0.103N     P=0.516     |                                                    |
|POLY 1.5           |     P=0.119      P=0.214N     P=0.101N     P=0.503     |                                                    |
|POLY 6             |     P=0.137      P=0.221N     P=0.110N     P=0.526     |                                                    |
|LOGISTIC REGRESSION|     P=0.120      P=0.213N     P=0.103N     P=0.500     |                                                    |
|COCH-ARM / FISHERS |     P=0.121      P=0.218N     P=0.102N     P=0.500     |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Cyst Epithelial Inclusion                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     5.4%         0.0%         0.0%         5.3%        |2.4%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/18 (6%)    0/16 (0%)    0/15 (0%)    0/15 (0%)   |1/29 (3%)    0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     723          ---          ---          588         |734 (T)      ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.295      P=0.282N     P=0.289N     P=0.647     |P=0.671N     P=0.493N     P=0.507N     P=0.514N     |
|POLY 3             |     P=0.308      P=0.232N     P=0.235N     P=0.686N    |P=0.662N     P=0.493N     P=0.504N     P=0.509N     |
|POLY 1.5           |     P=0.303      P=0.232N     P=0.234N     P=0.690N    |P=0.659N     P=0.496N     P=0.504N     P=0.507N     |
|POLY 6             |     P=0.315      P=0.236N     P=0.241N     P=0.686N    |P=0.663N     P=0.492N     P=0.504N     P=0.511N     |
|LOGISTIC REGRESSION|     P=0.307      P=0.260N     P=0.268N     P=0.693N    |P=0.671N     (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.305      P=0.247N     P=0.247N     P=0.691N    |P=0.657N     P=0.500N     P=0.500N     P=0.500N     |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 32
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    2/50 (4%)    0/50 (0%)   |1/50 (2%)    2/50 (4%)    0/50 (0%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         2.6%         5.3%         0.0%        |2.4%         4.6%         0.0%         4.8%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    0/15 (0%)    0/15 (0%)   |1/29 (3%)    1/30 (3%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     ---          588          518          ---         |734 (T)      727          ---          415          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.404N     P=0.516      P=0.247      (e)         |P=0.393      P=0.508      P=0.507N     P=0.489      |
|POLY 3             |     P=0.406N     P=0.507      P=0.243      (e)         |P=0.410      P=0.512      P=0.504N     P=0.494      |
|POLY 1.5           |     P=0.408N     P=0.505      P=0.243      (e)         |P=0.410      P=0.507      P=0.504N     P=0.494      |
|POLY 6             |     P=0.407N     P=0.505      P=0.240      (e)         |P=0.410      P=0.515      P=0.504N     P=0.495      |
|LOGISTIC REGRESSION|     P=0.379N     P=0.477      P=0.212      (e)         |P=0.444      P=0.507      (e)          P=0.576      |
|COCH-ARM / FISHERS |     P=0.408N     P=0.500      P=0.247      (e)         |P=0.414      P=0.500      P=0.500N     P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Fibrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     11/50 (22%)  14/50 (28%)  24/50 (48%)  22/50 (44%) |4/50 (8%)    6/50 (12%)   10/50 (20%)  4/50 (8%)    |
|POLY-3 ADJUSTED (b)|     28.5%        35.0%        59.0%        54.3%       |9.1%         13.3%        23.0%        9.7%         |
|TERMINAL (d)       |     3/18 (17%)   5/16 (31%)   10/15 (67%)  10/15 (67%) |0/29 (0%)    3/30 (10%)   4/28 (14%)   1/27 (4%)    |
|FIRST INCIDENCE    |     564          549          541          566         |539          370          508          594          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.071      P=0.283      P=0.005 **   P=0.017 *   |P=0.335N     P=0.395      P=0.082      P=0.604      |
|POLY 3             |     P=0.053      P=0.350      P=0.003 **   P=0.013 *   |P=0.325N     P=0.384      P=0.067      P=0.611      |
|POLY 1.5           |     P=0.050      P=0.347      P=0.004 **   P=0.013 *   |P=0.310N     P=0.381      P=0.068      P=0.619      |
|POLY 6             |     P=0.053      P=0.341      P=0.002 **   P=0.012 *   |P=0.337N     P=0.382      P=0.067      P=0.603      |
|LOGISTIC REGRESSION|     P=0.060      P=0.339      P=0.005 **   P=0.016 *   |P=0.246N     P=0.318      P=0.081      P=0.612N     |
|COCH-ARM / FISHERS |     P=0.063      P=0.322      P=0.006 **   P=0.016 *   |P=0.274N     P=0.370      P=0.074      P=0.643N     |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 33
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hematopoietic Cell Proliferation                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    3/50 (6%)    1/50 (2%)    5/50 (10%)  |4/50 (8%)    5/50 (10%)   0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     7.9%         7.7%         2.7%         12.7%       |8.9%         11.1%        0.0%         2.5%         |
|TERMINAL (d)       |     1/18 (6%)    0/16 (0%)    0/15 (0%)    0/15 (0%)   |0/29 (0%)    2/30 (7%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     454          398          684          478         |398          482          ---          714          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.180      P=0.652      P=0.326N     P=0.368     |P=0.196N     P=0.513      P=0.070N     P=0.207N     |
|POLY 3             |     P=0.178      P=0.652N     P=0.311N     P=0.376     |P=0.185N     P=0.503      P=0.070N     P=0.210N     |
|POLY 1.5           |     P=0.169      P=0.652N     P=0.305N     P=0.366     |P=0.179N     P=0.501      P=0.067N     P=0.200N     |
|POLY 6             |     P=0.188      P=0.662N     P=0.326N     P=0.379     |P=0.189N     P=0.506      P=0.072N     P=0.218N     |
|LOGISTIC REGRESSION|     P=0.197      P=0.609      P=0.318N     P=0.364     |P=0.113N     P=0.368      P=0.019N*    P=0.086N     |
|COCH-ARM / FISHERS |     P=0.167      P=0.661N     P=0.309N     P=0.357     |P=0.170N     P=0.500      P=0.059N     P=0.181N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hemorrhage                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    2/50 (4%)    4/50 (8%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     2.7%         0.0%         0.0%         0.0%        |2.3%         4.5%         9.3%         0.0%         |
|TERMINAL (d)       |     1/18 (6%)    0/16 (0%)    0/15 (0%)    0/15 (0%)   |0/29 (0%)    0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     733 (T)      ---          ---          ---         |657          370          547          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.674N     P=0.523N     P=0.536N     P=0.536N    |P=0.182N     P=0.515      P=0.174      P=0.516N     |
|POLY 3             |     P=0.658N     P=0.496N     P=0.499N     P=0.497N    |P=0.182N     P=0.517      P=0.179      P=0.511N     |
|POLY 1.5           |     P=0.660N     P=0.496N     P=0.497N     P=0.499N    |P=0.176N     P=0.511      P=0.177      P=0.508N     |
|POLY 6             |     P=0.652N     P=0.500N     P=0.505N     P=0.499N    |P=0.189N     P=0.521      P=0.182      P=0.514N     |
|LOGISTIC REGRESSION|     P=0.674N     (e)          (e)          (e)         |P=0.121N     P=0.439      P=0.194      P=0.492N     |
|COCH-ARM / FISHERS |     P=0.657N     P=0.500N     P=0.500N     P=0.500N    |P=0.162N     P=0.500      P=0.181      P=0.500N     |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 34
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    0/50 (0%)    2/50 (4%)    1/50 (2%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     8.0%         0.0%         5.3%         2.7%        |2.3%         0.0%         0.0%         2.4%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    0/15 (0%)    0/15 (0%)   |0/29 (0%)    0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     564          ---          537          668         |648          ---          ---          490          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.478N     P=0.134N     P=0.508N     P=0.321N    |P=0.499      P=0.495N     P=0.516N     P=0.750      |
|POLY 3             |     P=0.482N     P=0.118N     P=0.498N     P=0.305N    |P=0.499      P=0.495N     P=0.505N     P=0.753      |
|POLY 1.5           |     P=0.487N     P=0.116N     P=0.493N     P=0.306N    |P=0.502      P=0.497N     P=0.504N     P=0.754      |
|POLY 6             |     P=0.476N     P=0.124N     P=0.512N     P=0.312N    |P=0.497      P=0.494N     P=0.507N     P=0.751      |
|LOGISTIC REGRESSION|     P=0.477N     P=0.121N     P=0.510N     P=0.305N    |P=0.574      P=0.514N     P=0.490N     P=0.710N     |
|COCH-ARM / FISHERS |     P=0.481N     P=0.121N     P=0.500N     P=0.309N    |P=0.511      P=0.500N     P=0.500N     P=0.753N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         5.3%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    0/15 (0%)    0/15 (0%)   |0/29 (0%)    0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     ---          ---          566          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.552N     (e)          P=0.233      (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.556N     (e)          P=0.242      (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.558N     (e)          P=0.242      (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.556N     (e)          P=0.238      (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.553N     (e)          P=0.232      (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.557N     (e)          P=0.247      (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 35
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     14/50 (28%)  8/50 (16%)   10/50 (20%)  12/50 (24%) |5/50 (10%)   2/50 (4%)    7/50 (14%)   3/50 (6%)    |
|POLY-3 ADJUSTED (b)|     34.0%        19.9%        25.1%        29.2%       |11.3%        4.5%         16.0%        7.2%         |
|TERMINAL (d)       |     2/18 (11%)   0/16 (0%)    0/15 (0%)    1/15 (7%)   |0/29 (0%)    0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     440          510          518          478         |398          686          547          497          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.466      P=0.155N     P=0.294N     P=0.427N    |P=0.410N     P=0.210N     P=0.365      P=0.398N     |
|POLY 3             |     P=0.460      P=0.114N     P=0.258N     P=0.409N    |P=0.402N     P=0.218N     P=0.367      P=0.394N     |
|POLY 1.5           |     P=0.439      P=0.108N     P=0.242N     P=0.413N    |P=0.390N     P=0.217N     P=0.366      P=0.383N     |
|POLY 6             |     P=0.477      P=0.135N     P=0.295N     P=0.427N    |P=0.414N     P=0.219N     P=0.373      P=0.404N     |
|LOGISTIC REGRESSION|     P=0.453      P=0.123N     P=0.248N     P=0.409N    |P=0.289N     P=0.255N     P=0.433      P=0.274N     |
|COCH-ARM / FISHERS |     P=0.442      P=0.114N     P=0.241N     P=0.410N    |P=0.358N     P=0.218N     P=0.380      P=0.357N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Glandular                                                                                                               |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     5/50 (10%)   1/50 (2%)    4/50 (8%)    4/50 (8%)   |0/50 (0%)    0/49 (0%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     13.3%        2.7%         10.6%        10.6%       |0.0%         0.0%         2.4%         0.0%         |
|TERMINAL (d)       |     3/18 (17%)   1/16 (6%)    1/15 (7%)    1/15 (7%)   |0/29 (0%)    0/30 (0%)    1/28 (4%)    0/27 (0%)    |
|FIRST INCIDENCE    |     539          733 (T)      566          667         |---          ---          734 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.478      P=0.122N     P=0.555N     P=0.550N    |P=0.754N     (e)          P=0.493      (e)          |
|POLY 3             |     P=0.496      P=0.099N     P=0.496N     P=0.499N    |P=0.749N     (e)          P=0.496      (e)          |
|POLY 1.5           |     P=0.488      P=0.098N     P=0.491N     P=0.501N    |P=0.746N     (e)          P=0.496      (e)          |
|POLY 6             |     P=0.504      P=0.105N     P=0.513N     P=0.508N    |P=0.751N     (e)          P=0.496      (e)          |
|LOGISTIC REGRESSION|     P=0.498      P=0.099N     P=0.496N     P=0.494N    |(e)          (e)          P=0.493      (e)          |
|COCH-ARM / FISHERS |     P=0.494      P=0.102N     P=0.500N     P=0.500N    |P=0.739N     (e)          P=0.500      (e)          |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 36
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Glandular                                                                                                               |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     6/50 (12%)   3/50 (6%)    7/50 (14%)   9/50 (18%)  |3/50 (6%)    3/49 (6%)    4/50 (8%)    6/50 (12%)   |
|POLY-3 ADJUSTED (b)|     15.6%        7.8%         17.8%        22.0%       |6.9%         6.7%         9.4%         14.1%        |
|TERMINAL (d)       |     0/18 (0%)    0/16 (0%)    0/15 (0%)    0/15 (0%)   |0/29 (0%)    0/30 (0%)    0/28 (0%)    0/27 (0%)    |
|FIRST INCIDENCE    |     539          538          518          361         |552          587          566          464          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.151      P=0.273N     P=0.481      P=0.306     |P=0.151      P=0.633N     P=0.496      P=0.224      |
|POLY 3             |     P=0.142      P=0.236N     P=0.519      P=0.328     |P=0.158      P=0.652N     P=0.487      P=0.230      |
|POLY 1.5           |     P=0.129      P=0.234N     P=0.519      P=0.310     |P=0.162      P=0.660N     P=0.489      P=0.232      |
|POLY 6             |     P=0.156      P=0.249N     P=0.506      P=0.335     |P=0.154      P=0.645N     P=0.485      P=0.229      |
|LOGISTIC REGRESSION|     P=0.135      P=0.250N     P=0.489      P=0.290     |P=0.222      P=0.603      P=0.517      P=0.292      |
|COCH-ARM / FISHERS |     P=0.121      P=0.243N     P=0.500      P=0.288     |P=0.174      P=0.651      P=0.500      P=0.243      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes: Artery                                                                                                                   |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     6/50 (12%)   2/50 (4%)    1/50 (2%)    0/50 (0%)   |                                                    |
|POLY-3 ADJUSTED (b)|     16.1%        5.3%         2.7%         0.0%        |                                                    |
|TERMINAL (d)       |     3/18 (17%)   0/16 (0%)    0/15 (0%)    0/15 (0%)   |                                                    |
|FIRST INCIDENCE    |     664          664          712          ---         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.063N     P=0.170N     P=0.088N     P=0.026N*   |                                                    |
|POLY 3             |     P=0.052N     P=0.123N     P=0.054N     P=0.014N*   |                                                    |
|POLY 1.5           |     P=0.055N     P=0.124N     P=0.053N     P=0.015N*   |                                                    |
|POLY 6             |     P=0.050N     P=0.127N     P=0.059N     P=0.015N*   |                                                    |
|LOGISTIC REGRESSION|     P=0.054N     P=0.130N     P=0.062N     P=0.017N*   |                                                    |
|COCH-ARM / FISHERS |     P=0.056N     P=0.134N     P=0.056N     P=0.013N*   |                                                    |
|=================================================================================================================================|
       Date:  10/02/97                           EXPERIMENT: 05135 TEST: 07                                            Page 37
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER344)  -                      ISOPRENE
                                         Terminal Sacrifice at 104 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes: Interstitial Cell                                                                                                        |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     15/50 (30%)  13/50 (26%)  8/50 (16%)   0/50 (0%)   |                                                    |
|POLY-3 ADJUSTED (b)|     36.1%        30.0%        19.8%        0.0%        |                                                    |
|TERMINAL (d)       |     4/18 (22%)   2/16 (13%)   0/15 (0%)    0/15 (0%)   |                                                    |
|FIRST INCIDENCE    |     454          398          454          ---         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001N**   P=0.448N     P=0.119N     P<0.001N**  |                                                    |
|POLY 3             |     P<0.001N**   P=0.354N     P=0.075N     P<0.001N**  |                                                    |
|POLY 1.5           |     P<0.001N**   P=0.364N     P=0.071N     P<0.001N**  |                                                    |
|POLY 6             |     P<0.001N**   P=0.369N     P=0.090N     P<0.001N**  |                                                    |
|LOGISTIC REGRESSION|     P<0.001N**   P=0.476N     P=0.089N     P<0.001N**  |                                                    |
|COCH-ARM / FISHERS |     P<0.001N**   P=0.412N     P=0.077N     P<0.001N**  |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     CONTROL      220 PPM      700 PPM      7000 PPM    |CONTROL      220 PPM      700 PPM      7000 PPM     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|TUMOR RATES        |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     30/49 (61%)  30/50 (60%)  30/49 (61%)  34/50 (68%) |40/48 (83%)  32/50 (64%)  38/49 (78%)  40/50 (80%)  |
|POLY-3 ADJUSTED (b)|     70.4%        67.5%        69.9%        76.2%       |85.6%        67.6%        82.7%        89.7%        |
|TERMINAL (d)       |     11/18 (61%)  9/16 (56%)   10/15 (67%)  10/15 (67%) |25/29 (86%)  19/30 (63%)  23/28 (82%)  25/27 (93%)  |
|FIRST INCIDENCE    |     440          499          510          361         |398          482          427          490          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.243      P=0.464      P=0.414      P=0.228     |P=0.138      P=0.092N     P=0.519N     P=0.385      |
|POLY 3             |     P=0.227      P=0.471N     P=0.577N     P=0.349     |P=0.063      P=0.028N*    P=0.457N     P=0.381      |
|POLY 1.5           |     P=0.206      P=0.483N     P=0.560N     P=0.320     |P=0.109      P=0.027N*    P=0.426N     P=0.507      |
|POLY 6             |     P=0.238      P=0.470N     P=0.595      P=0.358     |P=0.041 *    P=0.030N*    P=0.490N     P=0.292      |
|LOGISTIC REGRESSION|     P=0.209      P=0.491N     P=0.550N     P=0.315     |P=0.179      P=0.024N*    P=0.362N     P=0.594N     |
|COCH-ARM / FISHERS |     P=0.227      P=0.532N     P=0.582N     P=0.310     |P=0.293      P=0.026N*    P=0.323N     P=0.435N     |
|=================================================================================================================================|

(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).