National Toxicology Program

National Toxicology Program
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TDMS Study 05135-06 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Northwest                                         ISOPRENE                                       DATE: 10/15/04       
EXPERIMENT: 05135 TEST: 06                                                                                     TIME: 13:31:40       
TEST TYPE:  SIX MONTH EXPOS.                                                                                   PAGE:       1        
CONT: N01-ES-55105                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: 61825C       
PATHOLOGIST: HAILEY, JAMES R.                PERSING, RONALD                                                   CAS: 78-79-5         
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
                                                                                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Northwest                                         ISOPRENE                                       DATE: 10/15/04       
EXPERIMENT: 05135 TEST: 06                                                                                     TIME: 13:31:40       
TEST TYPE:  SIX MONTH EXPOS.                                                                                                        
CONT: N01-ES-55105                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: 61825C       
PATHOLOGIST: HAILEY, JAMES R.                PERSING, RONALD                                                   CAS: 78-79-5         
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF                        ISOPRENE                                                                                  
===============================================================                                                                     
Male Mice                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Bone Marrow                            Hyperplasia                                                                                  
Brain                                  Hemorrhage                                                                                   
Islets, Pancreatic                     Hyperplasia                                                                                  
Liver                                  Eosinophilic Focus                                                                           
                                       Mixed Cell Focus                                                                             
                                       Necrosis                                                                                     
                                       Vacuolization Cytoplasmic                                                                    
Lung                                   Congestion                                                                                   
Lung: Alveolar Epithelium              Hyperplasia                                                                                  
Nose                                   Inflammation                                                                                 
Nose: Turbinate, Olfactory Epithelium  Degeneration                                                                                 
                                       Inflammation Chronic                                                                         
Pancreas                               Focal Cellular Change                                                                        
Peripheral Nerve: Sciatic              Degeneration                                                                                 
Pituitary Gland: Pars Distalis         Cyst                                                                                         
Preputial Gland                        Inflammation                                                                                 
Prostate                               Inflammation                                                                                 
Salivary Glands                        Inflammation                                                                                 
Skeletal Muscle                        Atrophy                                                                                      
Skin                                   Inflammation                                                                                 
Spinal Cord                            Degeneration                                                                                 
Spleen                                 Pigmentation Melanin                                                                         
Stomach, Forestomach: Epithelium       Hyperplasia                                                                                  
Stomach, Glandular                     Hyperplasia                                                                                  
                                       Inflammation                                                                                 
                                       Necrosis                                                                                     
Testes                                 Atrophy                                                                                      
Thymus                                 Necrosis                                                                                     
Urinary Bladder                        Dilatation                                                                                   
===============================================================                                                                     
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 1       
                     Statistical Analysis of Non-neoplastic Lesions in        Mice(B6C3F1)  -                         ISOPRENE      
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        6/40 (15%)       0/12 (0%)        0/11 (0%)        0/13 (0%)        8/39 (21%)       6/38 (16%)      | 
|POLY-3 RATE (b)    |        6/28.81          0/1.54           0/1.78           0/2.94           8/28.36          6/23.81         | 
|POLY-3 PERCENT (g) |        20.8%            0.0%             0.0%             0.0%             28.2%            25.2%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/9 (0%)         0/10 (0%)       | 
|TERMINAL (d)       |        6/27 (22%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         8/26 (31%)       6/21 (29%)      | 
|FIRST INCIDENCE    |        371 (T)          ---              ---              ---              371 (T)          371 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.427          P=1.000N         P=1.000          P=1.000N         P=0.348          P=0.434         | 
|POLY 3             |        P=0.427          P=0.577N         P=0.562N         P=0.478N         P=0.367          P=0.482         | 
|POLY 1.5           |        P=0.376          P=0.426N         P=0.413N         P=0.342N         P=0.368          P=0.516         | 
|POLY 6             |        P=0.426          P=0.664N         P=0.653N         P=0.569N         P=0.362          P=0.458         | 
|LOGISTIC REGRESSION|        P=0.427          (e)              (e)              (e)              P=0.348          P=0.434         | 
|COCH-ARM / FISHERS |        P=0.205          P=0.189N         P=0.213N         P=0.167N         P=0.365          P=0.585         | 
|ORDER RESTRICTED   |        P=0.230          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/40 (13%)       0/12 (0%)        0/11 (0%)        0/13 (0%)        6/39 (15%)       4/38 (11%)      | 
|POLY-3 RATE (b)    |        5/28.81          0/1.54           0/1.78           0/2.94           6/28.36          4/24.18         | 
|POLY-3 PERCENT (g) |        17.4%            0.0%             0.0%             0.0%             21.2%            16.5%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/9 (0%)         0/10 (0%)       | 
|TERMINAL (d)       |        5/27 (19%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         6/26 (23%)       3/21 (14%)      | 
|FIRST INCIDENCE    |        371 (T)          ---              ---              ---              371 (T)          317             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.555          P=1.000N         P=1.000          P=1.000N         P=0.472          P=0.630         | 
|POLY 3             |        P=0.571N         P=0.603N         P=0.591N         P=0.516N         P=0.489          P=0.612N        | 
|POLY 1.5           |        P=0.576          P=0.470N         P=0.460N         P=0.392N         P=0.489          P=0.589N        | 
|POLY 6             |        P=0.561N         P=0.678N         P=0.670N         P=0.595N         P=0.485          P=0.623N        | 
|LOGISTIC REGRESSION|        P=0.586          (e)              (e)              (e)              P=0.472          P=0.636N        | 
|COCH-ARM / FISHERS |        P=0.381          P=0.253N         P=0.280N         P=0.229N         P=0.482          P=0.533N        | 
|ORDER RESTRICTED   |        P=0.492          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 2       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone Marrow                                                                                                                      | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        0/12 (0%)        0/11 (0%)        1/13 (8%)        2/40 (5%)        4/38 (11%)      | 
|POLY-3 RATE (b)    |        1/29.33          0/1.54           0/1.78           1/3.28           2/28.80          4/24.63         | 
|POLY-3 PERCENT (g) |        3.4%             0.0%             0.0%             30.5%            6.9%             16.2%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/27 (0%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         1/26 (4%)        3/21 (14%)      | 
|FIRST INCIDENCE    |        289              ---              ---              324              326              209             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.029 *        P=0.500N         P=0.493N         P=0.748N         P=0.496          P=0.123         | 
|POLY 3             |        P=0.080          P=0.836N         P=0.842N         P=0.315          P=0.494          P=0.125         | 
|POLY 1.5           |        P=0.082          P=0.811N         P=0.817N         P=0.375          P=0.497          P=0.136         | 
|POLY 6             |        P=0.073          P=0.848N         P=0.854N         P=0.284          P=0.490          P=0.118         | 
|LOGISTIC REGRESSION|        P=0.091          P=0.814N         P=0.802N         P=0.416          P=0.499          P=0.146         | 
|COCH-ARM / FISHERS |        P=0.064          P=0.769N         P=0.784N         P=0.434          P=0.500          P=0.164         | 
|ORDER RESTRICTED   |        P=0.015 *        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain                                                                                                                            | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        0/12 (0%)        0/11 (0%)        2/13 (15%)       0/40 (0%)        0/38 (0%)       | 
|POLY-3 RATE (b)    |        0/28.81          0/1.54           0/1.78           2/3.87           0/28.48          0/23.81         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             51.7%            0.0%             0.0%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/27 (0%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/26 (0%)        0/21 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              176              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.591N         (e)              (e)              P=0.247          (e)              (e)             | 
|POLY 3             |        P=0.570N         (e)              (e)              P=0.013 *        (e)              (e)             | 
|POLY 1.5           |        P=0.488N         (e)              (e)              P=0.019 *        (e)              (e)             | 
|POLY 6             |        P=0.626N         (e)              (e)              P=0.011 *        (e)              (e)             | 
|LOGISTIC REGRESSION|        P=0.406N         (e)              (e)              P=0.043 *        (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.403N         (e)              (e)              P=0.057          (e)              (e)             | 
|ORDER RESTRICTED   |        P=0.051N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 3       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain                                                                                                                            | 
|     Mineralization                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        0/12 (0%)        0/11 (0%)        0/13 (0%)        2/40 (5%)        0/38 (0%)       | 
|POLY-3 RATE (b)    |        1/28.81          0/1.54           0/1.78           0/2.94           2/28.48          0/23.81         | 
|POLY-3 PERCENT (g) |        3.5%             0.0%             0.0%             0.0%             7.0%             0.0%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        1/27 (4%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         2/26 (8%)        0/21 (0%)       | 
|FIRST INCIDENCE    |        371 (T)          ---              ---              ---              371 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.380N         P=1.000N         P=1.000          P=1.000N         P=0.487          P=0.550N        | 
|POLY 3             |        P=0.370N         P=0.836N         P=0.842N         P=0.814N         P=0.496          P=0.538N        | 
|POLY 1.5           |        P=0.390N         P=0.811N         P=0.816N         P=0.786N         P=0.499          P=0.529N        | 
|POLY 6             |        P=0.370N         P=0.848N         P=0.854N         P=0.828N         P=0.493          P=0.544N        | 
|LOGISTIC REGRESSION|        P=0.380N         (e)              (e)              (e)              P=0.487          (e)             | 
|COCH-ARM / FISHERS |        P=0.472N         P=0.769N         P=0.784N         P=0.755N         P=0.500          P=0.513N        | 
|ORDER RESTRICTED   |        P=0.184N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        0/40 (0%)        3/39 (8%)        2/40 (5%)        3/40 (8%)        2/38 (5%)       | 
|POLY-3 RATE (b)    |        1/28.81          0/29.54          3/31.08          2/30.31          3/29.68          2/24.18         | 
|POLY-3 PERCENT (g) |        3.5%             0.0%             9.7%             6.6%             10.1%            8.3%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        1/10 (10%)       0/10 (0%)        1/10 (10%)       0/10 (0%)       | 
|TERMINAL (d)       |        1/27 (4%)        0/28 (0%)        1/28 (4%)        0/27 (0%)        1/26 (4%)        1/21 (5%)       | 
|FIRST INCIDENCE    |        371 (T)          ---              183 (I)          324              183 (I)          317             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.325          P=0.493N         P=0.321          P=0.512          P=0.301          P=0.423         | 
|POLY 3             |        P=0.315          P=0.495N         P=0.331          P=0.518          P=0.314          P=0.439         | 
|POLY 1.5           |        P=0.340          P=0.497N         P=0.321          P=0.513          P=0.311          P=0.451         | 
|POLY 6             |        P=0.303          P=0.494N         P=0.339          P=0.522          P=0.316          P=0.432         | 
|LOGISTIC REGRESSION|        P=0.388          (e)              P=0.291          P=0.512          P=0.304          P=0.437         | 
|COCH-ARM / FISHERS |        P=0.400          P=0.500N         P=0.298          P=0.500          P=0.308          P=0.481         | 
|ORDER RESTRICTED   |        P=0.252          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 4       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Islets, Pancreatic                                                                                                               | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        9/40 (23%)       9/40 (23%)       12/39 (31%)      12/40 (30%)      16/40 (40%)      13/38 (34%)     | 
|POLY-3 RATE (b)    |        9/28.81          9/29.54          12/29.78         12/29.94         16/28.48         13/23.81        | 
|POLY-3 PERCENT (g) |        31.2%            30.5%            40.3%            40.1%            56.2%            54.6%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        9/27 (33%)       9/28 (32%)       12/28 (43%)      12/27 (44%)      16/26 (62%)      13/21 (62%)     | 
|FIRST INCIDENCE    |        371 (T)          371 (T)          371 (T)          371 (T)          371 (T)          371 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.016 *        P=0.576N         P=0.328          P=0.290          P=0.039 *        P=0.048 *       | 
|POLY 3             |        P=0.032 *        P=0.587N         P=0.326          P=0.332          P=0.045 *        P=0.072         | 
|POLY 1.5           |        P=0.055          P=0.597N         P=0.314          P=0.326          P=0.052          P=0.099         | 
|POLY 6             |        P=0.022 *        P=0.580N         P=0.331          P=0.334          P=0.041 *        P=0.058         | 
|LOGISTIC REGRESSION|        P=0.016 *        P=0.576N         P=0.328          P=0.290          P=0.039 *        P=0.048 *       | 
|COCH-ARM / FISHERS |        P=0.154          P=0.605N         P=0.282          P=0.306          P=0.074          P=0.185         | 
|ORDER RESTRICTED   |        P=0.060          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Fibrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/40 (5%)        0/13 (0%)        0/11 (0%)        0/14 (0%)        0/40 (0%)        1/38 (3%)       | 
|POLY-3 RATE (b)    |        2/29.69          0/2.54           0/1.78           0/3.94           0/28.48          1/23.81         | 
|POLY-3 PERCENT (g) |        6.7%             0.0%             0.0%             0.0%             0.0%             4.2%            | 
|INT SACRIFICE 1 (c)|        1/10 (10%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        1/27 (4%)        0/1 (0%)         0/0 (0%)         0/1 (0%)         0/26 (0%)        1/21 (5%)       | 
|FIRST INCIDENCE    |        183 (I)          ---              ---              ---              ---              371 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.689N         P=0.473N         P=0.500N         P=0.473N         P=0.244N         P=0.558N        | 
|POLY 3             |        P=0.575N         P=0.703N         P=0.736N         P=0.661N         P=0.245N         P=0.577N        | 
|POLY 1.5           |        P=0.604N         P=0.644N         P=0.675N         P=0.602N         P=0.241N         P=0.558N        | 
|POLY 6             |        P=0.566N         P=0.735N         P=0.769N         P=0.695N         P=0.248N         P=0.588N        | 
|LOGISTIC REGRESSION|        P=0.667N         P=0.494N         P=0.526N         P=0.461N         P=0.237N         P=0.525N        | 
|COCH-ARM / FISHERS |        P=0.689N         P=0.566N         P=0.612N         P=0.545N         P=0.247N         P=0.519N        | 
|ORDER RESTRICTED   |        P=0.147N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 5       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Hydronephrosis                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/40 (5%)        1/13 (8%)        0/11 (0%)        1/14 (7%)        1/40 (3%)        1/38 (3%)       | 
|POLY-3 RATE (b)    |        2/29.69          1/2.54           0/1.78           1/3.97           1/29.36          1/23.81         | 
|POLY-3 PERCENT (g) |        6.7%             39.4%            0.0%             25.2%            3.4%             4.2%            | 
|INT SACRIFICE 1 (c)|        1/10 (10%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)       0/10 (0%)       | 
|TERMINAL (d)       |        1/27 (4%)        1/1 (100%)       0/0 (0%)         0/1 (0%)         0/26 (0%)        1/21 (5%)       | 
|FIRST INCIDENCE    |        183 (I)          371 (T)          ---              367              183 (I)          371 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.463N         P=0.551          P=0.500N         P=0.733N         P=0.504N         P=0.558N        | 
|POLY 3             |        P=0.434N         P=0.365          P=0.736N         P=0.425          P=0.504N         P=0.577N        | 
|POLY 1.5           |        P=0.401N         P=0.450          P=0.675N         P=0.505          P=0.501N         P=0.558N        | 
|POLY 6             |        P=0.467N         P=0.317          P=0.769N         P=0.376          P=0.507N         P=0.588N        | 
|LOGISTIC REGRESSION|        P=0.363N         P=0.538          P=0.526N         P=0.598          P=0.504N         P=0.525N        | 
|COCH-ARM / FISHERS |        P=0.396N         P=0.578          P=0.612N         P=0.602          P=0.500N         P=0.519N        | 
|ORDER RESTRICTED   |        P=0.166N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Bilateral                                                                                                                | 
|     Fibrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/40 (5%)        0/13 (0%)        0/11 (0%)        0/14 (0%)        0/40 (0%)        1/38 (3%)       | 
|POLY-3 RATE (b)    |        2/29.69          0/2.54           0/1.78           0/3.94           0/28.48          1/23.81         | 
|POLY-3 PERCENT (g) |        6.7%             0.0%             0.0%             0.0%             0.0%             4.2%            | 
|INT SACRIFICE 1 (c)|        1/10 (10%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        1/27 (4%)        0/1 (0%)         0/0 (0%)         0/1 (0%)         0/26 (0%)        1/21 (5%)       | 
|FIRST INCIDENCE    |        183 (I)          ---              ---              ---              ---              371 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.689N         P=0.473N         P=0.500N         P=0.473N         P=0.244N         P=0.558N        | 
|POLY 3             |        P=0.575N         P=0.703N         P=0.736N         P=0.661N         P=0.245N         P=0.577N        | 
|POLY 1.5           |        P=0.604N         P=0.644N         P=0.675N         P=0.602N         P=0.241N         P=0.558N        | 
|POLY 6             |        P=0.566N         P=0.735N         P=0.769N         P=0.695N         P=0.248N         P=0.588N        | 
|LOGISTIC REGRESSION|        P=0.667N         P=0.494N         P=0.526N         P=0.461N         P=0.237N         P=0.525N        | 
|COCH-ARM / FISHERS |        P=0.689N         P=0.566N         P=0.612N         P=0.545N         P=0.247N         P=0.519N        | 
|ORDER RESTRICTED   |        P=0.147N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 6       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Bilateral                                                                                                                | 
|     Hydronephrosis                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/40 (5%)        1/13 (8%)        0/11 (0%)        1/14 (7%)        1/40 (3%)        1/38 (3%)       | 
|POLY-3 RATE (b)    |        2/29.69          1/2.54           0/1.78           1/3.97           1/29.36          1/23.81         | 
|POLY-3 PERCENT (g) |        6.7%             39.4%            0.0%             25.2%            3.4%             4.2%            | 
|INT SACRIFICE 1 (c)|        1/10 (10%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)       0/10 (0%)       | 
|TERMINAL (d)       |        1/27 (4%)        1/1 (100%)       0/0 (0%)         0/1 (0%)         0/26 (0%)        1/21 (5%)       | 
|FIRST INCIDENCE    |        183 (I)          371 (T)          ---              367              183 (I)          371 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.463N         P=0.551          P=0.500N         P=0.733N         P=0.504N         P=0.558N        | 
|POLY 3             |        P=0.434N         P=0.365          P=0.736N         P=0.425          P=0.504N         P=0.577N        | 
|POLY 1.5           |        P=0.401N         P=0.450          P=0.675N         P=0.505          P=0.501N         P=0.558N        | 
|POLY 6             |        P=0.467N         P=0.317          P=0.769N         P=0.376          P=0.507N         P=0.588N        | 
|LOGISTIC REGRESSION|        P=0.363N         P=0.538          P=0.526N         P=0.598          P=0.504N         P=0.525N        | 
|COCH-ARM / FISHERS |        P=0.396N         P=0.578          P=0.612N         P=0.602          P=0.500N         P=0.519N        | 
|ORDER RESTRICTED   |        P=0.166N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Bilateral, Renal Tubule                                                                                                  | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        0/13 (0%)        0/11 (0%)        0/14 (0%)        2/40 (5%)        0/38 (0%)       | 
|POLY-3 RATE (b)    |        1/28.81          0/2.54           0/1.78           0/3.94           2/28.48          0/23.81         | 
|POLY-3 PERCENT (g) |        3.5%             0.0%             0.0%             0.0%             7.0%             0.0%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        1/27 (4%)        0/1 (0%)         0/0 (0%)         0/1 (0%)         2/26 (8%)        0/21 (0%)       | 
|FIRST INCIDENCE    |        371 (T)          ---              ---              ---              371 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.394N         P=0.994N         P=1.000          P=0.994N         P=0.487          P=0.550N        | 
|POLY 3             |        P=0.377N         P=0.818N         P=0.842N         P=0.795N         P=0.496          P=0.538N        | 
|POLY 1.5           |        P=0.400N         P=0.792N         P=0.816N         P=0.768N         P=0.499          P=0.529N        | 
|POLY 6             |        P=0.374N         P=0.831N         P=0.854N         P=0.810N         P=0.493          P=0.544N        | 
|LOGISTIC REGRESSION|        P=0.394N         (e)              (e)              (e)              P=0.487          (e)             | 
|COCH-ARM / FISHERS |        P=0.478N         P=0.755N         P=0.784N         P=0.741N         P=0.500          P=0.513N        | 
|ORDER RESTRICTED   |        P=0.198N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 7       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        0/13 (0%)        0/11 (0%)        0/14 (0%)        2/40 (5%)        0/38 (0%)       | 
|POLY-3 RATE (b)    |        1/28.81          0/2.54           0/1.78           0/3.94           2/28.48          0/23.81         | 
|POLY-3 PERCENT (g) |        3.5%             0.0%             0.0%             0.0%             7.0%             0.0%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        1/27 (4%)        0/1 (0%)         0/0 (0%)         0/1 (0%)         2/26 (8%)        0/21 (0%)       | 
|FIRST INCIDENCE    |        371 (T)          ---              ---              ---              371 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.394N         P=0.994N         P=1.000          P=0.994N         P=0.487          P=0.550N        | 
|POLY 3             |        P=0.377N         P=0.818N         P=0.842N         P=0.795N         P=0.496          P=0.538N        | 
|POLY 1.5           |        P=0.400N         P=0.792N         P=0.816N         P=0.768N         P=0.499          P=0.529N        | 
|POLY 6             |        P=0.374N         P=0.831N         P=0.854N         P=0.810N         P=0.493          P=0.544N        | 
|LOGISTIC REGRESSION|        P=0.394N         (e)              (e)              (e)              P=0.487          (e)             | 
|COCH-ARM / FISHERS |        P=0.478N         P=0.755N         P=0.784N         P=0.741N         P=0.500          P=0.513N        | 
|ORDER RESTRICTED   |        P=0.198N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Angiectasis                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        0/40 (0%)        0/39 (0%)        2/40 (5%)        1/40 (3%)        2/38 (5%)       | 
|POLY-3 RATE (b)    |        0/28.81          0/29.54          0/29.78          2/29.94          1/28.48          2/24.18         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             6.7%             3.5%             8.3%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/27 (0%)        0/28 (0%)        0/28 (0%)        2/27 (7%)        1/26 (4%)        1/21 (5%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              371 (T)          371 (T)          317             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.064          (e)              (e)              P=0.238          P=0.492          P=0.196         | 
|POLY 3             |        P=0.075          (e)              (e)              P=0.244          P=0.498          P=0.198         | 
|POLY 1.5           |        P=0.082          (e)              (e)              P=0.243          P=0.499          P=0.206         | 
|POLY 6             |        P=0.072          (e)              (e)              P=0.245          P=0.496          P=0.194         | 
|LOGISTIC REGRESSION|        P=0.069          (e)              (e)              P=0.238          P=0.492          P=0.202         | 
|COCH-ARM / FISHERS |        P=0.102          (e)              (e)              P=0.247          P=0.500          P=0.234         | 
|ORDER RESTRICTED   |        P=0.068          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 8       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Basophilic Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        3/40 (8%)        1/40 (3%)        2/39 (5%)        4/40 (10%)       5/40 (13%)       4/38 (11%)      | 
|POLY-3 RATE (b)    |        3/28.81          1/29.54          2/30.66          4/31.70          5/28.48          4/24.69         | 
|POLY-3 PERCENT (g) |        10.4%            3.4%             6.5%             12.6%            17.6%            16.2%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        1/10 (10%)       2/10 (20%)       0/10 (0%)        1/10 (10%)      | 
|TERMINAL (d)       |        3/27 (11%)       1/28 (4%)        1/28 (4%)        2/27 (7%)        5/26 (19%)       3/21 (14%)      | 
|FIRST INCIDENCE    |        371 (T)          371 (T)          183 (I)          183 (I)          371 (T)          183 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.130          P=0.290N         P=0.487N         P=0.500          P=0.331          P=0.382         | 
|POLY 3             |        P=0.132          P=0.294N         P=0.471N         P=0.553          P=0.346          P=0.414         | 
|POLY 1.5           |        P=0.152          P=0.298N         P=0.482N         P=0.539          P=0.351          P=0.432         | 
|POLY 6             |        P=0.120          P=0.292N         P=0.466N         P=0.560          P=0.341          P=0.402         | 
|LOGISTIC REGRESSION|        P=0.171          P=0.290N         P=0.500N         P=0.502          P=0.331          P=0.413         | 
|COCH-ARM / FISHERS |        P=0.207          P=0.308N         P=0.512N         P=0.500          P=0.356          P=0.471         | 
|ORDER RESTRICTED   |        P=0.223          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Clear Cell Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        0/40 (0%)        0/39 (0%)        2/40 (5%)        0/40 (0%)        1/38 (3%)       | 
|POLY-3 RATE (b)    |        0/28.81          0/29.54          0/29.78          2/29.94          0/28.48          1/23.81         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             6.7%             0.0%             4.2%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/27 (0%)        0/28 (0%)        0/28 (0%)        2/27 (7%)        0/26 (0%)        1/21 (5%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              371 (T)          ---              371 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.345          (e)              (e)              P=0.238          (e)              P=0.450         | 
|POLY 3             |        P=0.356          (e)              (e)              P=0.244          (e)              P=0.462         | 
|POLY 1.5           |        P=0.371          (e)              (e)              P=0.243          (e)              P=0.471         | 
|POLY 6             |        P=0.346          (e)              (e)              P=0.245          (e)              P=0.456         | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.238          (e)              P=0.450         | 
|COCH-ARM / FISHERS |        P=0.404          (e)              (e)              P=0.247          (e)              P=0.487         | 
|ORDER RESTRICTED   |        P=0.237          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 9       
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Eosinophilic Focus                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        0/40 (0%)        0/39 (0%)        6/40 (15%)       5/40 (13%)       3/38 (8%)       | 
|POLY-3 RATE (b)    |        1/28.81          0/29.54          0/29.78          6/29.94          5/28.48          3/23.81         | 
|POLY-3 PERCENT (g) |        3.5%             0.0%             0.0%             20.0%            17.6%            12.6%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        1/27 (4%)        0/28 (0%)        0/28 (0%)        6/27 (22%)       5/26 (19%)       3/21 (14%)      | 
|FIRST INCIDENCE    |        371 (T)          ---              ---              371 (T)          371 (T)          371 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.084          P=0.493N         P=0.493N         P=0.054          P=0.091          P=0.217         | 
|POLY 3             |        P=0.087          P=0.495N         P=0.493N         P=0.057          P=0.093          P=0.237         | 
|POLY 1.5           |        P=0.107          P=0.497N         P=0.496N         P=0.056          P=0.095          P=0.252         | 
|POLY 6             |        P=0.077          P=0.494N         P=0.492N         P=0.057          P=0.091          P=0.227         | 
|LOGISTIC REGRESSION|        P=0.084          (e)              (e)              P=0.054          P=0.091          P=0.217         | 
|COCH-ARM / FISHERS |        P=0.166          P=0.500N         P=0.506N         P=0.054          P=0.100          P=0.288         | 
|ORDER RESTRICTED   |        P=0.034 *        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        0/40 (0%)        0/39 (0%)        0/40 (0%)        2/40 (5%)        1/38 (3%)       | 
|POLY-3 RATE (b)    |        0/28.81          0/29.54          0/29.78          0/29.94          2/28.80          1/23.81         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             6.9%             4.2%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/27 (0%)        0/28 (0%)        0/28 (0%)        0/27 (0%)        1/26 (4%)        1/21 (5%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              326              371 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.124          (e)              (e)              (e)              P=0.236          P=0.450         | 
|POLY 3             |        P=0.120          (e)              (e)              (e)              P=0.236          P=0.462         | 
|POLY 1.5           |        P=0.134          (e)              (e)              (e)              P=0.236          P=0.471         | 
|POLY 6             |        P=0.112          (e)              (e)              (e)              P=0.235          P=0.456         | 
|LOGISTIC REGRESSION|        P=0.137          (e)              (e)              (e)              P=0.235          P=0.450         | 
|COCH-ARM / FISHERS |        P=0.170          (e)              (e)              (e)              P=0.247          P=0.487         | 
|ORDER RESTRICTED   |        P=0.108          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 10      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Mixed Cell Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        0/40 (0%)        1/39 (3%)        1/40 (3%)        2/40 (5%)        3/38 (8%)       | 
|POLY-3 RATE (b)    |        0/28.81          0/29.54          1/29.78          1/29.94          2/28.48          3/23.81         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             3.4%             3.3%             7.0%             12.6%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/27 (0%)        0/28 (0%)        1/28 (4%)        1/27 (4%)        2/26 (8%)        3/21 (14%)      | 
|FIRST INCIDENCE    |        ---              ---              371 (T)          371 (T)          371 (T)          371 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.011 *        (e)              P=0.507          P=0.500          P=0.229          P=0.079         | 
|POLY 3             |        P=0.016 *        (e)              P=0.507          P=0.508          P=0.233          P=0.085         | 
|POLY 1.5           |        P=0.019 *        (e)              P=0.504          P=0.506          P=0.235          P=0.091         | 
|POLY 6             |        P=0.015 *        (e)              P=0.508          P=0.508          P=0.231          P=0.080         | 
|LOGISTIC REGRESSION|        (e)              (e)              P=0.507          P=0.500          P=0.229          P=0.079         | 
|COCH-ARM / FISHERS |        P=0.027 *        (e)              P=0.494          P=0.500          P=0.247          P=0.111         | 
|ORDER RESTRICTED   |        P=0.018 *        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        0/40 (0%)        1/39 (3%)        1/40 (3%)        0/40 (0%)        2/38 (5%)       | 
|POLY-3 RATE (b)    |        0/28.81          0/29.54          1/29.78          1/29.97          0/28.48          2/24.77         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             3.4%             3.3%             0.0%             8.1%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/27 (0%)        0/28 (0%)        1/28 (4%)        0/27 (0%)        0/26 (0%)        1/21 (5%)       | 
|FIRST INCIDENCE    |        ---              ---              371 (T)          367              ---              128             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.083          (e)              P=0.507          P=0.507          (e)              P=0.207         | 
|POLY 3             |        P=0.098          (e)              P=0.507          P=0.508          (e)              P=0.203         | 
|POLY 1.5           |        P=0.103          (e)              P=0.504          P=0.506          (e)              P=0.210         | 
|POLY 6             |        P=0.095          (e)              P=0.508          P=0.509          (e)              P=0.198         | 
|LOGISTIC REGRESSION|        P=0.113          (e)              P=0.507          P=0.508          (e)              P=0.250         | 
|COCH-ARM / FISHERS |        P=0.113          (e)              P=0.494          P=0.500          (e)              P=0.234         | 
|ORDER RESTRICTED   |        P=0.044 *        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 11      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Vacuolization Cytoplasmic                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        22/40 (55%)      25/40 (63%)      27/39 (69%)      20/40 (50%)      24/40 (60%)      14/38 (37%)     | 
|POLY-3 RATE (b)    |        22/30.57         25/31.30         27/32.42         20/33.46         24/31.12         14/27.41        | 
|POLY-3 PERCENT (g) |        72.0%            79.9%            83.3%            59.8%            77.1%            51.1%           | 
|INT SACRIFICE 1 (c)|        2/10 (20%)       2/10 (20%)       3/10 (30%)       4/10 (40%)       3/10 (30%)       3/10 (30%)      | 
|TERMINAL (d)       |        20/27 (74%)      23/28 (82%)      24/28 (86%)      16/27 (59%)      21/26 (81%)      10/21 (48%)     | 
|FIRST INCIDENCE    |        183 (I)          183 (I)          183 (I)          183 (I)          183 (I)          128             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.068N         P=0.367          P=0.187          P=0.403N         P=0.314          P=0.212N        | 
|POLY 3             |        P=0.011N*        P=0.326          P=0.205          P=0.217N         P=0.428          P=0.077N        | 
|POLY 1.5           |        P=0.008N**       P=0.311          P=0.178          P=0.266N         P=0.427          P=0.073N        | 
|POLY 6             |        P=0.015N*        P=0.338          P=0.222          P=0.196N         P=0.417          P=0.085N        | 
|LOGISTIC REGRESSION|        P=0.029N*        P=0.336          P=0.173          P=0.352N         P=0.382          P=0.135N        | 
|COCH-ARM / FISHERS |        P=0.009N**       P=0.325          P=0.142          P=0.412N         P=0.411          P=0.083N        | 
|ORDER RESTRICTED   |        P=0.012N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Congestion                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        3/40 (8%)        0/40 (0%)        0/39 (0%)        0/40 (0%)        0/40 (0%)        2/38 (5%)       | 
|POLY-3 RATE (b)    |        3/28.81          0/29.54          0/29.78          0/29.94          0/28.48          2/24.77         | 
|POLY-3 PERCENT (g) |        10.4%            0.0%             0.0%             0.0%             0.0%             8.1%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        3/27 (11%)       0/28 (0%)        0/28 (0%)        0/27 (0%)        0/26 (0%)        1/21 (5%)       | 
|FIRST INCIDENCE    |        371 (T)          ---              ---              ---              ---              123             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.217          P=0.113N         P=0.113N         P=0.120N         P=0.126N         P=0.594N        | 
|POLY 3             |        P=0.237          P=0.111N         P=0.110N         P=0.109N         P=0.118N         P=0.569N        | 
|POLY 1.5           |        P=0.246          P=0.114N         P=0.113N         P=0.111N         P=0.117N         P=0.554N        | 
|POLY 6             |        P=0.231          P=0.110N         P=0.109N         P=0.109N         P=0.119N         P=0.581N        | 
|LOGISTIC REGRESSION|        P=0.259          (e)              (e)              (e)              (e)              P=0.547N        | 
|COCH-ARM / FISHERS |        P=0.271          P=0.120N         P=0.125N         P=0.120N         P=0.120N         P=0.525N        | 
|ORDER RESTRICTED   |        P=0.041N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 12      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        3/40 (8%)        2/40 (5%)        2/39 (5%)        1/40 (3%)        2/40 (5%)        2/38 (5%)       | 
|POLY-3 RATE (b)    |        3/30.57          2/30.54          2/29.78          1/29.97          2/29.40          2/23.81         | 
|POLY-3 PERCENT (g) |        9.8%             6.6%             6.7%             3.3%             6.8%             8.4%            | 
|INT SACRIFICE 1 (c)|        1/10 (10%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        1/27 (4%)        1/28 (4%)        2/28 (7%)        0/27 (0%)        1/26 (4%)        2/21 (10%)      | 
|FIRST INCIDENCE    |        182              16               371 (T)          367              160              371 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.552          P=0.493N         P=0.488N         P=0.305N         P=0.509N         P=0.580N        | 
|POLY 3             |        P=0.534          P=0.500N         P=0.512N         P=0.310N         P=0.518N         P=0.613N        | 
|POLY 1.5           |        P=0.560          P=0.498N         P=0.510N         P=0.307N         P=0.510N         P=0.585N        | 
|POLY 6             |        P=0.517          P=0.501N         P=0.514N         P=0.313N         P=0.525N         P=0.630N        | 
|LOGISTIC REGRESSION|        P=0.574N         P=0.490N         P=0.526N         P=0.319N         P=0.503N         P=0.519N        | 
|COCH-ARM / FISHERS |        P=0.603N         P=0.500N         P=0.512N         P=0.308N         P=0.500N         P=0.525N        | 
|ORDER RESTRICTED   |        P=0.548N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolar Epithelium                                                                                                        | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        1/40 (3%)        0/39 (0%)        3/40 (8%)        5/40 (13%)       7/38 (18%)      | 
|POLY-3 RATE (b)    |        1/29.69          1/29.54          0/29.78          3/29.94          5/29.36          7/23.81         | 
|POLY-3 PERCENT (g) |        3.4%             3.4%             0.0%             10.0%            17.0%            29.4%           | 
|INT SACRIFICE 1 (c)|        1/10 (10%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)       0/10 (0%)       | 
|TERMINAL (d)       |        0/27 (0%)        1/28 (4%)        0/28 (0%)        3/27 (11%)       4/26 (15%)       7/21 (33%)      | 
|FIRST INCIDENCE    |        183 (I)          371 (T)          ---              371 (T)          183 (I)          371 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.756N         P=0.500N         P=0.306          P=0.098          P=0.013 *       | 
|POLY 3             |        P<0.001 **       P=0.760          P=0.499N         P=0.306          P=0.094          P=0.010 *       | 
|POLY 1.5           |        P<0.001 **       P=0.760          P=0.500N         P=0.307          P=0.096          P=0.013 *       | 
|POLY 6             |        P<0.001 **       P=0.761          P=0.499N         P=0.305          P=0.092          P=0.008 **      | 
|LOGISTIC REGRESSION|        P<0.001 **       P=0.763          P=0.584N         P=0.307          P=0.101          P=0.016 *       | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.753N         P=0.506N         P=0.308          P=0.100          P=0.024 *       | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 13      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mesentery                                                                                                                        | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/1 (100%)       2/2 (100%)       0/0 (0%)         2/2 (100%)       2/4 (50%)        2/2 (100%)      | 
|POLY-3 RATE (b)    |        1/1.00           2/2.00           0/0.00           2/2.00           2/3.15           2/2.00          | 
|POLY-3 PERCENT (g) |        100.0%           100.0%           0.0%             100.0%           63.5%            100.0%          | 
|INT SACRIFICE 1 (c)|        1/1 (100%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|TERMINAL (d)       |        0/0 (0%)         2/2 (100%)       0/0 (0%)         1/1 (100%)       2/2 (100%)       2/2 (100%)      | 
|FIRST INCIDENCE    |        183 (I)          371 (T)          ---              367              371 (T)          371 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.762N         (e)              (e)              (e)              P=1.000          (e)             | 
|POLY 3             |        (e)              (e)              (e)              (e)              P=0.730N         (e)             | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              P=0.648N         (e)             | 
|POLY 6             |        (e)              (e)              (e)              (e)              P=0.892N         (e)             | 
|LOGISTIC REGRESSION|        P=0.727N         (e)              (e)              (e)              P=0.688N         (e)             | 
|COCH-ARM / FISHERS |        P=0.778          (e)              (e)              (e)              P=0.600N         (e)             | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose                                                                                                                             | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        0/40 (0%)        0/39 (0%)        0/40 (0%)        0/40 (0%)        2/38 (5%)       | 
|POLY-3 RATE (b)    |        0/28.81          0/29.54          0/29.78          0/29.94          0/28.48          2/24.63         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             8.1%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/27 (0%)        0/28 (0%)        0/28 (0%)        0/27 (0%)        0/26 (0%)        1/21 (5%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              209             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.005 **       (e)              (e)              (e)              (e)              P=0.196         | 
|POLY 3             |        P=0.006 **       (e)              (e)              (e)              (e)              P=0.202         | 
|POLY 1.5           |        P=0.007 **       (e)              (e)              (e)              (e)              P=0.208         | 
|POLY 6             |        P=0.006 **       (e)              (e)              (e)              (e)              P=0.197         | 
|LOGISTIC REGRESSION|        P=0.010 *        (e)              (e)              (e)              (e)              P=0.229         | 
|COCH-ARM / FISHERS |        P=0.008 **       (e)              (e)              (e)              (e)              P=0.234         | 
|ORDER RESTRICTED   |        P=0.005 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 14      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose: Turbinate, Olfactory Epithelium                                                                                            | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        2/40 (5%)        5/39 (13%)       12/40 (30%)      26/40 (65%)      38/38 (100%)    | 
|POLY-3 RATE (b)    |        1/29.79          2/29.54          5/29.78          12/30.82         26/30.60         38/38.00        | 
|POLY-3 PERCENT (g) |        3.4%             6.8%             16.8%            38.9%            85.0%            100.0%          | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)       1/10 (10%)       10/10 (100%)    | 
|TERMINAL (d)       |        0/27 (0%)        2/28 (7%)        5/28 (18%)       11/27 (41%)      23/26 (89%)      21/21 (100%)    | 
|FIRST INCIDENCE    |        90               371 (T)          371 (T)          183 (I)          160              123             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.505          P=0.110          P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 3             |        P<0.001 **       P=0.497          P=0.096          P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       P=0.495          P=0.095          P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 6             |        P<0.001 **       P=0.498          P=0.097          P<0.001 **       P<0.001 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        P<0.001 **       P=0.500          P=0.098          P<0.001 **       P<0.001 **       P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.500          P=0.095          P<0.001 **       P<0.001 **       P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose: Turbinate, Olfactory Epithelium                                                                                            | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        0/40 (0%)        0/39 (0%)        0/40 (0%)        1/40 (3%)        30/38 (79%)     | 
|POLY-3 RATE (b)    |        0/28.81          0/29.54          0/29.78          0/29.94          1/28.48          30/30.74        | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             3.5%             97.6%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        5/10 (50%)      | 
|TERMINAL (d)       |        0/27 (0%)        0/28 (0%)        0/28 (0%)        0/27 (0%)        1/26 (4%)        21/21 (100%)    | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              371 (T)          128             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              (e)              P=0.492          P<0.001 **      | 
|POLY 3             |        P<0.001 **       (e)              (e)              (e)              P=0.498          P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              (e)              P=0.499          P<0.001 **      | 
|POLY 6             |        P<0.001 **       (e)              (e)              (e)              P=0.496          P<0.001 **      | 
|LOGISTIC REGRESSION|        P<0.001 **       (e)              (e)              (e)              P=0.492          P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              (e)              P=0.500          P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 15      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas                                                                                                                         | 
|     Focal Cellular Change                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/40 (5%)        1/40 (3%)        0/39 (0%)        5/40 (13%)       3/40 (8%)        6/38 (16%)      | 
|POLY-3 RATE (b)    |        2/28.81          1/29.54          0/29.78          5/29.94          3/28.48          6/23.81         | 
|POLY-3 PERCENT (g) |        6.9%             3.4%             0.0%             16.7%            10.5%            25.2%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        2/27 (7%)        1/28 (4%)        0/28 (0%)        5/27 (19%)       3/26 (12%)       6/21 (29%)      | 
|FIRST INCIDENCE    |        371 (T)          371 (T)          ---              371 (T)          371 (T)          371 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.003 **       P=0.487N         P=0.230N         P=0.211          P=0.482          P=0.061         | 
|POLY 3             |        P=0.005 **       P=0.491N         P=0.228N         P=0.227          P=0.495          P=0.072         | 
|POLY 1.5           |        P=0.007 **       P=0.495N         P=0.232N         P=0.224          P=0.498          P=0.083         | 
|POLY 6             |        P=0.004 **       P=0.489N         P=0.227N         P=0.227          P=0.491          P=0.065         | 
|LOGISTIC REGRESSION|        P=0.003 **       P=0.487N         (e)              P=0.211          P=0.482          P=0.061         | 
|COCH-ARM / FISHERS |        P=0.013 *        P=0.500N         P=0.253N         P=0.216          P=0.500          P=0.115         | 
|ORDER RESTRICTED   |        P=0.008 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas                                                                                                                         | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        2/40 (5%)        0/39 (0%)        0/40 (0%)        1/40 (3%)        1/38 (3%)       | 
|POLY-3 RATE (b)    |        0/28.81          2/29.54          0/29.78          0/29.94          1/28.48          1/24.18         | 
|POLY-3 PERCENT (g) |        0.0%             6.8%             0.0%             0.0%             3.5%             4.1%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/27 (0%)        2/28 (7%)        0/28 (0%)        0/27 (0%)        1/26 (4%)        0/21 (0%)       | 
|FIRST INCIDENCE    |        ---              371 (T)          ---              ---              371 (T)          317             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.415          P=0.246          (e)              (e)              P=0.492          P=0.468         | 
|POLY 3             |        P=0.422          P=0.241          (e)              (e)              P=0.498          P=0.465         | 
|POLY 1.5           |        P=0.436          P=0.239          (e)              (e)              P=0.499          P=0.472         | 
|POLY 6             |        P=0.415          P=0.243          (e)              (e)              P=0.496          P=0.462         | 
|LOGISTIC REGRESSION|        P=0.429          P=0.246          (e)              (e)              P=0.492          P=0.482         | 
|COCH-ARM / FISHERS |        P=0.475          P=0.247          (e)              (e)              P=0.500          P=0.487         | 
|ORDER RESTRICTED   |        P=0.307          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 16      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Peripheral Nerve: Sciatic                                                                                                        | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        0/40 (0%)        0/39 (0%)        1/39 (3%)        1/38 (3%)        5/38 (13%)      | 
|POLY-3 RATE (b)    |        0/28.81          0/29.54          0/29.78          1/28.94          1/27.33          5/27.70         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             3.5%             3.7%             18.1%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        2/10 (20%)      | 
|TERMINAL (d)       |        0/27 (0%)        0/28 (0%)        0/28 (0%)        1/26 (4%)        1/26 (4%)        0/21 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              371 (T)          371 (T)          146             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.492          P=0.492          P=0.028 *       | 
|POLY 3             |        P<0.001 **       (e)              (e)              P=0.501          P=0.489          P=0.024 *       | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P=0.500          P=0.489          P=0.024 *       | 
|POLY 6             |        P<0.001 **       (e)              (e)              P=0.501          P=0.491          P=0.025 *       | 
|LOGISTIC REGRESSION|        P<0.001 **       (e)              (e)              P=0.492          P=0.492          P=0.042 *       | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P=0.494          P=0.487          P=0.024 *       | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/38 (5%)        0/12 (0%)        1/10 (10%)       0/13 (0%)        0/37 (0%)        0/35 (0%)       | 
|POLY-3 RATE (b)    |        2/27.33          0/1.54           1/2.08           0/2.94           0/27.24          0/21.18         | 
|POLY-3 PERCENT (g) |        7.3%             0.0%             48.1%            0.0%             0.0%             0.0%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/9 (0%)         0/10 (0%)        0/8 (0%)         0/10 (0%)       | 
|TERMINAL (d)       |        1/25 (4%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/25 (0%)        0/19 (0%)       | 
|FIRST INCIDENCE    |        289              ---              309              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.233N         P=0.500N         P=0.748N         P=0.493N         P=0.240N         P=0.293N        | 
|POLY 3             |        P=0.174N         P=0.728N         P=0.342          P=0.683N         P=0.236N         P=0.296N        | 
|POLY 1.5           |        P=0.162N         P=0.664N         P=0.421          P=0.617N         P=0.237N         P=0.282N        | 
|POLY 6             |        P=0.187N         P=0.762N         P=0.301          P=0.721N         P=0.238N         P=0.305N        | 
|LOGISTIC REGRESSION|        P=0.151N         P=0.801N         P=0.393          P=0.682N         P=0.238N         P=0.273N        | 
|COCH-ARM / FISHERS |        P=0.178N         P=0.574N         P=0.512          P=0.551N         P=0.253N         P=0.268N        | 
|ORDER RESTRICTED   |        P=0.012N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 17      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Preputial Gland                                                                                                                  | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        3/13 (23%)       0/11 (0%)        0/16 (0%)        1/39 (3%)        0/37 (0%)       | 
|POLY-3 RATE (b)    |        1/28.81          3/5.08           0/1.78           0/5.94           1/28.01          0/22.81         | 
|POLY-3 PERCENT (g) |        3.5%             59.1%            0.0%             0.0%             3.6%             0.0%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        1/10 (10%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        1/27 (4%)        0/1 (0%)         0/0 (0%)         0/3 (0%)         1/26 (4%)        0/20 (0%)       | 
|FIRST INCIDENCE    |        371 (T)          16               ---              ---              371 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.179N         P=0.140          P=1.000N         P=0.909N         P=0.754          P=0.560N        | 
|POLY 3             |        P=0.177N         P=0.007 **       P=0.842N         P=0.760N         P=0.755          P=0.546N        | 
|POLY 1.5           |        P=0.147N         P=0.011 *        P=0.816N         P=0.734N         P=0.756          P=0.537N        | 
|POLY 6             |        P=0.200N         P=0.005 **       P=0.854N         P=0.775N         P=0.755          P=0.553N        | 
|LOGISTIC REGRESSION|        P=0.151N         P=0.141          (e)              (e)              P=0.754          (e)             | 
|COCH-ARM / FISHERS |        P=0.134N         P=0.042 *        P=0.784N         P=0.714N         P=0.747          P=0.519N        | 
|ORDER RESTRICTED   |        P=0.010N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Prostate                                                                                                                         | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/38 (0%)        0/12 (0%)        0/11 (0%)        0/13 (0%)        2/39 (5%)        0/37 (0%)       | 
|POLY-3 RATE (b)    |        0/27.33          0/1.54           0/1.78           0/2.94           2/27.48          0/22.81         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             7.3%             0.0%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/26 (0%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         2/25 (8%)        0/20 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              371 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.629N         (e)              (e)              (e)              P=0.229          (e)             | 
|POLY 3             |        P=0.654N         (e)              (e)              (e)              P=0.237          (e)             | 
|POLY 1.5           |        P=0.659N         (e)              (e)              (e)              P=0.240          (e)             | 
|POLY 6             |        P=0.662N         (e)              (e)              (e)              P=0.232          (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              P=0.229          (e)             | 
|COCH-ARM / FISHERS |        P=0.699N         (e)              (e)              (e)              P=0.253          (e)             | 
|ORDER RESTRICTED   |        P=0.190          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 18      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Prostate                                                                                                                         | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/38 (0%)        0/12 (0%)        0/11 (0%)        2/13 (15%)       0/39 (0%)        0/37 (0%)       | 
|POLY-3 RATE (b)    |        0/27.33          0/1.54           0/1.78           2/3.31           0/27.48          0/22.81         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             60.5%            0.0%             0.0%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/26 (0%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/25 (0%)        0/20 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              324              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.605N         (e)              (e)              P=0.252          (e)              (e)             | 
|POLY 3             |        P=0.596N         (e)              (e)              P=0.013 *        (e)              (e)             | 
|POLY 1.5           |        P=0.506N         (e)              (e)              P=0.020 *        (e)              (e)             | 
|POLY 6             |        P=0.648N         (e)              (e)              P=0.011 *        (e)              (e)             | 
|LOGISTIC REGRESSION|        P=0.353N         (e)              (e)              P<0.001 **       (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.403N         (e)              (e)              P=0.061          (e)              (e)             | 
|ORDER RESTRICTED   |        P=0.048N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Salivary Glands                                                                                                                  | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/40 (5%)        0/12 (0%)        0/11 (0%)        0/13 (0%)        0/40 (0%)        0/38 (0%)       | 
|POLY-3 RATE (b)    |        2/28.81          0/1.54           0/1.78           0/2.94           0/28.48          0/23.81         | 
|POLY-3 PERCENT (g) |        6.9%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        2/27 (7%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/26 (0%)        0/21 (0%)       | 
|FIRST INCIDENCE    |        371 (T)          ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.216N         P=1.000N         P=1.000N         P=1.000N         P=0.246N         P=0.294N        | 
|POLY 3             |        P=0.170N         P=0.734N         P=0.735N         P=0.690N         P=0.238N         P=0.280N        | 
|POLY 1.5           |        P=0.192N         P=0.673N         P=0.673N         P=0.627N         P=0.237N         P=0.270N        | 
|POLY 6             |        P=0.164N         P=0.767N         P=0.769N         P=0.726N         P=0.240N         P=0.288N        | 
|LOGISTIC REGRESSION|        P=0.216N         (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.273N         P=0.588N         P=0.612N         P=0.566N         P=0.247N         P=0.260N        | 
|ORDER RESTRICTED   |        P=0.016N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 19      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skeletal Muscle                                                                                                                  | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        0/40 (0%)        0/39 (0%)        0/40 (0%)        0/40 (0%)        4/38 (11%)      | 
|POLY-3 RATE (b)    |        0/28.81          0/29.54          0/29.78          0/29.94          0/28.48          4/27.33         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             14.6%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        4/10 (40%)      | 
|TERMINAL (d)       |        0/27 (0%)        0/28 (0%)        0/28 (0%)        0/27 (0%)        0/26 (0%)        0/21 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              183 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              (e)              (e)              P=0.051         | 
|POLY 3             |        P<0.001 **       (e)              (e)              (e)              (e)              P=0.050         | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              (e)              (e)              P=0.050         | 
|POLY 6             |        P<0.001 **       (e)              (e)              (e)              (e)              P=0.050         | 
|LOGISTIC REGRESSION|        P<0.001 **       (e)              (e)              (e)              (e)              P=0.082         | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              (e)              (e)              P=0.052         | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        2/14 (14%)       0/11 (0%)        0/14 (0%)        0/40 (0%)        1/39 (3%)       | 
|POLY-3 RATE (b)    |        0/28.81          2/4.20           0/1.78           0/3.94           0/28.48          1/24.66         | 
|POLY-3 PERCENT (g) |        0.0%             47.6%            0.0%             0.0%             0.0%             4.1%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/27 (0%)        1/2 (50%)        0/0 (0%)         0/1 (0%)         0/26 (0%)        0/21 (0%)       | 
|FIRST INCIDENCE    |        ---              259              ---              ---              ---              209             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.589          P=0.050          (e)              (e)              (e)              P=0.469         | 
|POLY 3             |        P=0.540          P=0.017 *        (e)              (e)              (e)              P=0.469         | 
|POLY 1.5           |        P=0.603          P=0.023 *        (e)              (e)              (e)              P=0.476         | 
|POLY 6             |        P=0.499          P=0.014 *        (e)              (e)              (e)              P=0.465         | 
|LOGISTIC REGRESSION|        P=0.691          P=0.011 *        (e)              (e)              (e)              P=0.547         | 
|COCH-ARM / FISHERS |        P=0.690          P=0.064          (e)              (e)              (e)              P=0.494         | 
|ORDER RESTRICTED   |        P=0.166          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 20      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin: Prepuce                                                                                                                    | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/40 (5%)        1/14 (7%)        0/11 (0%)        1/14 (7%)        2/40 (5%)        2/39 (5%)       | 
|POLY-3 RATE (b)    |        2/29.33          1/3.54           0/1.78           1/4.28           2/29.01          2/23.84         | 
|POLY-3 PERCENT (g) |        6.8%             28.2%            0.0%             23.4%            6.9%             8.4%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        1/27 (4%)        1/2 (50%)        0/0 (0%)         0/1 (0%)         1/26 (4%)        2/21 (10%)      | 
|FIRST INCIDENCE    |        289              371 (T)          ---              324              289              371 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.557          P=0.589          P=0.493N         P=0.725N         P=0.686          P=0.606         | 
|POLY 3             |        P=0.610          P=0.409          P=0.735N         P=0.438          P=0.692          P=0.618         | 
|POLY 1.5           |        P=0.623N         P=0.489          P=0.674N         P=0.513          P=0.694          P=0.640         | 
|POLY 6             |        P=0.582          P=0.363          P=0.769N         P=0.397          P=0.689          P=0.602         | 
|LOGISTIC REGRESSION|        P=0.557N         P=0.417          P=0.777N         P=0.517          P=0.695          P=0.635         | 
|COCH-ARM / FISHERS |        P=0.612          P=0.602          P=0.612N         P=0.602          P=0.692N         P=0.683         | 
|ORDER RESTRICTED   |        P=0.581          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spinal Cord                                                                                                                      | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/40 (10%)       20/40 (50%)      19/39 (49%)      28/40 (70%)      18/39 (46%)      23/38 (61%)     | 
|POLY-3 RATE (b)    |        4/28.81          20/29.54         19/29.78         28/30.31         18/28.89         23/34.74        | 
|POLY-3 PERCENT (g) |        13.9%            67.7%            63.8%            92.4%            62.3%            66.2%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)       10/10 (100%)    | 
|TERMINAL (d)       |        4/27 (15%)       20/28 (71%)      19/28 (68%)      26/27 (96%)      17/26 (65%)      10/21 (48%)     | 
|FIRST INCIDENCE    |        371 (T)          371 (T)          371 (T)          324              183 (I)          146             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 3             |        P=0.163          P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 1.5           |        P=0.071          P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 6             |        P=0.246          P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        P=0.002 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|COCH-ARM / FISHERS |        P=0.023 *        P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 21      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/40 (5%)        1/15 (7%)        0/11 (0%)        0/13 (0%)        2/40 (5%)        4/38 (11%)      | 
|POLY-3 RATE (b)    |        2/29.33          1/4.54           0/1.78           0/2.94           2/28.80          4/23.81         | 
|POLY-3 PERCENT (g) |        6.8%             22.0%            0.0%             0.0%             6.9%             16.8%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        1/27 (4%)        1/3 (33%)        0/0 (0%)         0/0 (0%)         1/26 (4%)        4/21 (19%)      | 
|FIRST INCIDENCE    |        289              371 (T)          ---              ---              326              371 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.140          P=0.621          P=0.493N         P=0.493N         P=0.686          P=0.231         | 
|POLY 3             |        P=0.164          P=0.450          P=0.735N         P=0.691N         P=0.689          P=0.242         | 
|POLY 1.5           |        P=0.163          P=0.522          P=0.674N         P=0.629N         P=0.692          P=0.264         | 
|POLY 6             |        P=0.155          P=0.406          P=0.769N         P=0.727N         P=0.686          P=0.226         | 
|LOGISTIC REGRESSION|        P=0.199          P=0.480          P=0.777N         P=0.689N         P=0.695          P=0.248         | 
|COCH-ARM / FISHERS |        P=0.131          P=0.623          P=0.612N         P=0.566N         P=0.692N         P=0.313         | 
|ORDER RESTRICTED   |        P=0.089          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Pigmentation Melanin                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        3/15 (20%)       0/11 (0%)        1/13 (8%)        1/40 (3%)        0/38 (0%)       | 
|POLY-3 RATE (b)    |        1/28.81          3/5.42           0/1.78           1/3.82           1/29.36          0/23.81         | 
|POLY-3 PERCENT (g) |        3.5%             55.4%            0.0%             26.2%            3.4%             0.0%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        1/10 (10%)       0/10 (0%)        1/10 (10%)       1/10 (10%)       0/10 (0%)       | 
|TERMINAL (d)       |        1/27 (4%)        2/3 (67%)        0/0 (0%)         0/0 (0%)         0/26 (0%)        0/21 (0%)       | 
|FIRST INCIDENCE    |        371 (T)          183 (I)          ---              183 (I)          183 (I)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.120N         P=0.008 **       P=1.000          P=0.500          P=0.756          P=0.550N        | 
|POLY 3             |        P=0.166N         P=0.011 *        P=0.842N         P=0.333          P=0.757N         P=0.538N        | 
|POLY 1.5           |        P=0.129N         P=0.017 *        P=0.816N         P=0.389          P=0.758N         P=0.529N        | 
|POLY 6             |        P=0.202N         P=0.008 **       P=0.854N         P=0.299          P=0.758N         P=0.544N        | 
|LOGISTIC REGRESSION|        P=0.101N         P=0.007 **       (e)              P=0.518          P=0.763          (e)             | 
|COCH-ARM / FISHERS |        P=0.101N         P=0.057          P=0.784N         P=0.434          P=0.753N         P=0.513N        | 
|ORDER RESTRICTED   |        P=0.010N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 22      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Angiectasis                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        0/40 (0%)        0/39 (0%)        0/40 (0%)        2/40 (5%)        0/38 (0%)       | 
|POLY-3 RATE (b)    |        0/28.81          0/29.54          0/29.78          0/29.94          2/28.48          0/23.81         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             7.0%             0.0%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/27 (0%)        0/28 (0%)        0/28 (0%)        0/27 (0%)        2/26 (8%)        0/21 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              371 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.615          (e)              (e)              (e)              P=0.229          (e)             | 
|POLY 3             |        P=0.557          (e)              (e)              (e)              P=0.233          (e)             | 
|POLY 1.5           |        P=0.587          (e)              (e)              (e)              P=0.235          (e)             | 
|POLY 6             |        P=0.539          (e)              (e)              (e)              P=0.231          (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              P=0.229          (e)             | 
|COCH-ARM / FISHERS |        P=0.649          (e)              (e)              (e)              P=0.247          (e)             | 
|ORDER RESTRICTED   |        P=0.187          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach: Epithelium                                                                                                 | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        2/40 (5%)        0/39 (0%)        16/40 (40%)      19/40 (48%)      15/38 (39%)     | 
|POLY-3 RATE (b)    |        1/28.81          2/29.54          0/29.78          16/38.21         19/38.20         15/33.63        | 
|POLY-3 PERCENT (g) |        3.5%             6.8%             0.0%             41.9%            49.7%            44.6%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        8/10 (80%)       10/10 (100%)     9/10 (90%)      | 
|TERMINAL (d)       |        1/27 (4%)        2/28 (7%)        0/28 (0%)        6/27 (22%)       8/26 (31%)       4/21 (19%)      | 
|FIRST INCIDENCE    |        371 (T)          371 (T)          ---              176              160              123             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.513          P=0.493N         P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 3             |        P<0.001 **       P=0.509          P=0.493N         P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       P=0.505          P=0.496N         P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 6             |        P<0.001 **       P=0.511          P=0.492N         P<0.001 **       P<0.001 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        P<0.001 **       P=0.513          (e)              P<0.001 **       P<0.001 **       P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.500          P=0.506N         P<0.001 **       P<0.001 **       P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 23      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular                                                                                                               | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        1/40 (3%)        0/39 (0%)        3/40 (8%)        2/38 (5%)        4/37 (11%)      | 
|POLY-3 RATE (b)    |        0/28.81          1/29.54          0/29.78          3/29.94          2/27.89          4/23.77         | 
|POLY-3 PERCENT (g) |        0.0%             3.4%             0.0%             10.0%            7.2%             16.8%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/9 (0%)         0/10 (0%)       | 
|TERMINAL (d)       |        0/27 (0%)        1/28 (4%)        0/28 (0%)        3/27 (11%)       2/26 (8%)        4/21 (19%)      | 
|FIRST INCIDENCE    |        ---              371 (T)          ---              371 (T)          371 (T)          371 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.007 **       P=0.507          (e)              P=0.120          P=0.229          P=0.034 *       | 
|POLY 3             |        P=0.010 *        P=0.505          (e)              P=0.123          P=0.228          P=0.036 *       | 
|POLY 1.5           |        P=0.012 *        P=0.503          (e)              P=0.122          P=0.227          P=0.040 *       | 
|POLY 6             |        P=0.009 **       P=0.506          (e)              P=0.123          P=0.229          P=0.033 *       | 
|LOGISTIC REGRESSION|        (e)              P=0.507          (e)              P=0.120          P=0.229          P=0.034 *       | 
|COCH-ARM / FISHERS |        P=0.018 *        P=0.500          (e)              P=0.120          P=0.234          P=0.049 *       | 
|ORDER RESTRICTED   |        P=0.009 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular                                                                                                               | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        1/40 (3%)        0/39 (0%)        1/40 (3%)        0/38 (0%)        2/37 (5%)       | 
|POLY-3 RATE (b)    |        0/28.81          1/30.42          0/29.78          1/30.28          0/27.89          2/23.77         | 
|POLY-3 PERCENT (g) |        0.0%             3.3%             0.0%             3.3%             0.0%             8.4%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        1/10 (10%)       0/10 (0%)        0/10 (0%)        0/9 (0%)         0/10 (0%)       | 
|TERMINAL (d)       |        0/27 (0%)        0/28 (0%)        0/28 (0%)        0/27 (0%)        0/26 (0%)        2/21 (10%)      | 
|FIRST INCIDENCE    |        ---              183 (I)          ---              324              ---              371 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.091          P=0.500          (e)              P=0.514          (e)              P=0.184         | 
|POLY 3             |        P=0.097          P=0.511          (e)              P=0.510          (e)              P=0.194         | 
|POLY 1.5           |        P=0.102          P=0.507          (e)              P=0.507          (e)              P=0.202         | 
|POLY 6             |        P=0.094          P=0.513          (e)              P=0.512          (e)              P=0.189         | 
|LOGISTIC REGRESSION|        P=0.113          P=0.527          (e)              P=0.502          (e)              P=0.184         | 
|COCH-ARM / FISHERS |        P=0.114          P=0.500          (e)              P=0.500          (e)              P=0.228         | 
|ORDER RESTRICTED   |        P=0.040 *        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 24      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular                                                                                                               | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        0/40 (0%)        0/39 (0%)        0/40 (0%)        0/38 (0%)        2/37 (5%)       | 
|POLY-3 RATE (b)    |        0/28.81          0/29.54          0/29.78          0/29.94          0/27.89          2/25.67         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             7.8%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/9 (0%)         0/10 (0%)       | 
|TERMINAL (d)       |        0/27 (0%)        0/28 (0%)        0/28 (0%)        0/27 (0%)        0/26 (0%)        0/21 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              128             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.007 **       (e)              (e)              (e)              (e)              P=0.222         | 
|POLY 3             |        P=0.006 **       (e)              (e)              (e)              (e)              P=0.210         | 
|POLY 1.5           |        P=0.007 **       (e)              (e)              (e)              (e)              P=0.214         | 
|POLY 6             |        P=0.006 **       (e)              (e)              (e)              (e)              P=0.206         | 
|LOGISTIC REGRESSION|        P=0.009 **       (e)              (e)              (e)              (e)              P=0.196         | 
|COCH-ARM / FISHERS |        P=0.008 **       (e)              (e)              (e)              (e)              P=0.228         | 
|ORDER RESTRICTED   |        P=0.006 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        0/40 (0%)        1/39 (3%)        0/40 (0%)        0/40 (0%)        8/39 (21%)      | 
|POLY-3 RATE (b)    |        0/28.81          0/29.54          1/30.66          0/29.94          0/28.48          8/30.96         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             3.3%             0.0%             0.0%             25.8%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        1/10 (10%)       0/10 (0%)        0/10 (0%)        5/10 (50%)      | 
|TERMINAL (d)       |        0/27 (0%)        0/28 (0%)        0/28 (0%)        0/27 (0%)        0/26 (0%)        0/21 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              183 (I)          ---              ---              128             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              P=0.500          (e)              (e)              P=0.003 **      | 
|POLY 3             |        P<0.001 **       (e)              P=0.512          (e)              (e)              P=0.004 **      | 
|POLY 1.5           |        P<0.001 **       (e)              P=0.508          (e)              (e)              P=0.003 **      | 
|POLY 6             |        P<0.001 **       (e)              P=0.515          (e)              (e)              P=0.004 **      | 
|LOGISTIC REGRESSION|        P<0.001 **       (e)              P=0.416          (e)              (e)              P=0.008 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              P=0.494          (e)              (e)              P=0.002 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 25      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        2/12 (17%)       0/11 (0%)        0/13 (0%)        0/39 (0%)        1/36 (3%)       | 
|POLY-3 RATE (b)    |        0/28.81          2/3.20           0/1.78           0/2.94           0/28.36          1/24.66         | 
|POLY-3 PERCENT (g) |        0.0%             62.5%            0.0%             0.0%             0.0%             4.1%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/9 (0%)         0/10 (0%)       | 
|TERMINAL (d)       |        0/27 (0%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/26 (0%)        0/21 (0%)       | 
|FIRST INCIDENCE    |        ---              16               ---              ---              ---              128             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.509          P=0.244          (e)              (e)              (e)              P=0.484         | 
|POLY 3             |        P=0.521          P=0.009 **       (e)              (e)              (e)              P=0.469         | 
|POLY 1.5           |        P=0.602          P=0.014 *        (e)              (e)              (e)              P=0.473         | 
|POLY 6             |        P=0.466          P=0.008 **       (e)              (e)              (e)              P=0.465         | 
|LOGISTIC REGRESSION|        P=0.510          P=0.246          (e)              (e)              (e)              P=0.430         | 
|COCH-ARM / FISHERS |        P=0.680          P=0.050          (e)              (e)              (e)              P=0.474         | 
|ORDER RESTRICTED   |        P=0.151          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Urinary Bladder                                                                                                                  | 
|     Dilatation                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        2/15 (13%)       0/11 (0%)        1/13 (8%)        0/40 (0%)        0/38 (0%)       | 
|POLY-3 RATE (b)    |        1/29.33          2/4.54           0/1.78           1/3.28           0/28.48          0/23.81         | 
|POLY-3 PERCENT (g) |        3.4%             44.1%            0.0%             30.5%            0.0%             0.0%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/27 (0%)        2/3 (67%)        0/0 (0%)         0/0 (0%)         0/26 (0%)        0/21 (0%)       | 
|FIRST INCIDENCE    |        289              371 (T)          ---              324              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.162N         P=0.110          P=0.493N         P=0.748N         P=0.500N         P=0.539N        | 
|POLY 3             |        P=0.238N         P=0.071          P=0.842N         P=0.315          P=0.506N         P=0.541N        | 
|POLY 1.5           |        P=0.183N         P=0.098          P=0.817N         P=0.375          P=0.503N         P=0.531N        | 
|POLY 6             |        P=0.284N         P=0.059          P=0.854N         P=0.284          P=0.510N         P=0.549N        | 
|LOGISTIC REGRESSION|        P=0.105N         P=0.035 *        P=0.802N         P=0.416          P=0.500N         P=0.505N        | 
|COCH-ARM / FISHERS |        P=0.133N         P=0.177          P=0.784N         P=0.434          P=0.500N         P=0.513N        | 
|ORDER RESTRICTED   |        P=0.011N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 06                                            Page 26      
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                         ISOPRENE       
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Urinary Bladder                                                                                                                  | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/40 (5%)        0/15 (0%)        0/11 (0%)        0/13 (0%)        0/40 (0%)        1/38 (3%)       | 
|POLY-3 RATE (b)    |        2/28.81          0/4.54           0/1.78           0/2.94           0/28.48          1/24.77         | 
|POLY-3 PERCENT (g) |        6.9%             0.0%             0.0%             0.0%             0.0%             4.0%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        2/27 (7%)        0/3 (0%)         0/0 (0%)         0/0 (0%)         0/26 (0%)        0/21 (0%)       | 
|FIRST INCIDENCE    |        371 (T)          ---              ---              ---              ---              128             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.694          P=0.764N         P=1.000          P=1.000N         P=0.246N         P=0.564N        | 
|POLY 3             |        P=0.577N         P=0.637N         P=0.735N         P=0.690N         P=0.238N         P=0.553N        | 
|POLY 1.5           |        P=0.608N         P=0.584N         P=0.673N         P=0.627N         P=0.237N         P=0.541N        | 
|POLY 6             |        P=0.565N         P=0.668N         P=0.769N         P=0.726N         P=0.240N         P=0.562N        | 
|LOGISTIC REGRESSION|        P=0.686N         (e)              (e)              (e)              (e)              P=0.510N        | 
|COCH-ARM / FISHERS |        P=0.693N         P=0.525N         P=0.612N         P=0.566N         P=0.247N         P=0.519N        | 
|ORDER RESTRICTED   |        P=0.123N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
(a)  Number of tumor-bearing animals /  number of animals examined at site.                                                         
(b)  Number of tumor-bearing animals / Poly-3 number                                                                                
(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.                                                                                         
(g)  Poly-3 adjusted lifetime tumor incidence.                                                                                      
(I)  Interim sacrifice                                                                                                              
(T)  Terminal sacrifice                                                                                                             
#   Tumor rates based on number of animals necropsied.                                                                              
*   To the right of any statistical result, indicates significance at (P<=0.05).                                                    
**  To the right of any statistical result, indicates significance at (P<=0.01).                                                    
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.