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TDMS Study 05135-03 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Northwest                                         ISOPRENE                                       DATE: 10/15/04       
EXPERIMENT: 05135 TEST: 03                                                                                     TIME: 13:06:20       
TEST TYPE:  SUBCHRON 90-DAY                                                                                    PAGE:       1        
CONT: N01-ES-55105                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C61825       
PATHOLOGIST: HAILEY, JAMES R.                                                                                  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: 03                                                                                     TIME: 13:06:20       
TEST TYPE:  SUBCHRON 90-DAY                                                                                                         
CONT: N01-ES-55105                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C61825       
PATHOLOGIST: HAILEY, JAMES R.                                                                                  CAS: 78-79-5         
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF                        ISOPRENE                                                                                  
===============================================================                                                                     
Male Rats                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Heart                                  Cardiomyopathy Focal                                                                         
Lung: Alveolar Epithelium              Hyperplasia Focal                                                                            
Lung: Alveolus                         Infiltration Cellular Focal Histiocyte                                                       
                                       Inflammation Focal                                                                           
Lung: Peribronchial                    Hyperplasia Focal Lymphoid                                                                   
Lung: Perivascular                     Hyperplasia Focal Lymphoid                                                                   
Lymph Node, Bronchial                  Hyperplasia                                                                                  
Lymph Node, Mediastinal                Hyperplasia                                                                                  
Pancreas                               Accessory Spleen                                                                             
===============================================================                                                                     
Female Rats                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Heart                                  Cardiomyopathy Focal                                                                         
Kidney                                 Mineralization Focal                                                                         
Kidney: Bilateral                      Mineralization Focal                                                                         
Lung: Alveolar Epithelium              Hyperplasia Focal                                                                            
Lung: Alveolus                         Infiltration Cellular Focal Histiocyte                                                       
                                       Inflammation Focal                                                                           
Lung: Peribronchial                    Hyperplasia Focal Lymphoid                                                                   
Lung: Perivascular                     Hyperplasia Focal Lymphoid                                                                   
Lymph Node, Bronchial                  Hyperplasia                                                                                  
===============================================================                                                                     
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 03                                            Page 1       
                     Statistical Analysis of Non-neoplastic Lesions in        Rats(FISCHER 344)  -                         ISOPRENE 
                                         Terminal Sacrifice at 14 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart                                                                                                                            | 
|     Cardiomyopathy Focal                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/10 (50%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        5/10 (50%)      | 
|POLY-3 RATE (b)    |        5/10.00          0/10.00          0/10.00          0/10.00          0/10.00          5/10.00         | 
|POLY-3 PERCENT (g) |        50.0%            0.0%             0.0%             0.0%             0.0%             50.0%           | 
|TERMINAL (d)       |        5/10 (50%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        5/10 (50%)      | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              ---              93 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.015 *        P=0.022N*        P=0.022N*        P=0.022N*        P=0.022N*        P=0.669         | 
|POLY 3             |        P=0.004 **       P=0.008N**       P=0.008N**       P=0.008N**       P=0.008N**       P=0.664         | 
|POLY 1.5           |        P=0.004 **       P=0.008N**       P=0.008N**       P=0.008N**       P=0.008N**       P=0.664         | 
|POLY 6             |        P=0.004 **       P=0.008N**       P=0.008N**       P=0.008N**       P=0.008N**       P=0.664         | 
|LOGISTIC REGRESSION|        P=0.015 *        (e)              (e)              (e)              (e)              P=0.669         | 
|COCH-ARM / FISHERS |        P=0.015 *        P=0.016N*        P=0.016N*        P=0.016N*        P=0.016N*        P=0.672N        | 
|ORDER RESTRICTED   |        P=0.002 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart                                                                                                                            | 
|     Cardiomyopathy Focal                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/10 (20%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|POLY-3 RATE (b)    |        2/10.00          0/10.00          0/10.00          0/10.00          0/10.00          0/10.00         | 
|POLY-3 PERCENT (g) |        20.0%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        2/10 (20%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.387N         P=0.234N         P=0.234N         P=0.234N         P=0.234N         P=0.234N        | 
|POLY 3             |        P=0.382N         P=0.227N         P=0.227N         P=0.227N         P=0.227N         P=0.227N        | 
|POLY 1.5           |        P=0.382N         P=0.227N         P=0.227N         P=0.227N         P=0.227N         P=0.227N        | 
|POLY 6             |        P=0.382N         P=0.227N         P=0.227N         P=0.227N         P=0.227N         P=0.227N        | 
|LOGISTIC REGRESSION|        P=0.387N         (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.387N         P=0.237N         P=0.237N         P=0.237N         P=0.237N         P=0.237N        | 
|ORDER RESTRICTED   |        P=0.007N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 03                                            Page 2       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 14 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Mineralization Focal                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|POLY-3 RATE (b)    |        0/10.00          0/10.00          0/10.00          0/10.00          0/10.00          0/10.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Mineralization Focal                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        9/10 (90%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)       8/10 (80%)      | 
|POLY-3 RATE (b)    |        9/10.00          0/10.00          0/10.00          0/10.00          1/10.00          8/10.00         | 
|POLY-3 PERCENT (g) |        90.0%            0.0%             0.0%             0.0%             10.0%            80.0%           | 
|TERMINAL (d)       |        9/10 (90%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)       8/10 (80%)      | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              93 (T)           93 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.002 **       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P=0.500N        | 
|POLY 3             |        P<0.001 **       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P=0.500N        | 
|POLY 1.5           |        P<0.001 **       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P=0.500N        | 
|POLY 6             |        P<0.001 **       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P=0.500N        | 
|LOGISTIC REGRESSION|        P=0.002 **       (e)              (e)              (e)              P<0.001N**       P=0.500N        | 
|COCH-ARM / FISHERS |        P=0.002 **       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P=0.500N        | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 03                                            Page 3       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 14 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Bilateral                                                                                                                | 
|     Mineralization Focal                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|POLY-3 RATE (b)    |        0/10.00          0/10.00          0/10.00          0/10.00          0/10.00          0/10.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Bilateral                                                                                                                | 
|     Mineralization Focal                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        9/10 (90%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)       8/10 (80%)      | 
|POLY-3 RATE (b)    |        9/10.00          0/10.00          0/10.00          0/10.00          1/10.00          8/10.00         | 
|POLY-3 PERCENT (g) |        90.0%            0.0%             0.0%             0.0%             10.0%            80.0%           | 
|TERMINAL (d)       |        9/10 (90%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)       8/10 (80%)      | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              93 (T)           93 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.002 **       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P=0.500N        | 
|POLY 3             |        P<0.001 **       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P=0.500N        | 
|POLY 1.5           |        P<0.001 **       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P=0.500N        | 
|POLY 6             |        P<0.001 **       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P=0.500N        | 
|LOGISTIC REGRESSION|        P=0.002 **       (e)              (e)              (e)              P<0.001N**       P=0.500N        | 
|COCH-ARM / FISHERS |        P=0.002 **       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P=0.500N        | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 03                                            Page 4       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 14 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatodiaphragmatic Nodule                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/10 (10%)       0/10 (0%)        2/10 (20%)       1/10 (10%)       0/10 (0%)        1/10 (10%)      | 
|POLY-3 RATE (b)    |        1/10.00          0/10.00          2/10.00          1/10.00          0/10.00          1/10.00         | 
|POLY-3 PERCENT (g) |        10.0%            0.0%             20.0%            10.0%            0.0%             10.0%           | 
|TERMINAL (d)       |        1/10 (10%)       0/10 (0%)        2/10 (20%)       1/10 (10%)       0/10 (0%)        1/10 (10%)      | 
|FIRST INCIDENCE    |        93 (T)           ---              93 (T)           93 (T)           ---              93 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.649N         P=0.500N         P=0.500          P=0.766          P=0.500N         P=0.766         | 
|POLY 3             |        P=0.647N         P=0.500N         P=0.500          P=0.760          P=0.500N         P=0.760         | 
|POLY 1.5           |        P=0.647N         P=0.500N         P=0.500          P=0.760          P=0.500N         P=0.760         | 
|POLY 6             |        P=0.647N         P=0.500N         P=0.500          P=0.760          P=0.500N         P=0.760         | 
|LOGISTIC REGRESSION|        P=0.649N         (e)              P=0.500          P=0.766          (e)              P=0.766         | 
|COCH-ARM / FISHERS |        P=0.650N         P=0.500N         P=0.500          P=0.763N         P=0.500N         P=0.763N        | 
|ORDER RESTRICTED   |        P=0.622          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatodiaphragmatic Nodule                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/10 (10%)       1/10 (10%)       1/10 (10%)       0/10 (0%)        0/10 (0%)        3/10 (30%)      | 
|POLY-3 RATE (b)    |        1/10.00          1/10.00          1/10.00          0/10.00          0/10.00          3/10.00         | 
|POLY-3 PERCENT (g) |        10.0%            10.0%            10.0%            0.0%             0.0%             30.0%           | 
|TERMINAL (d)       |        1/10 (10%)       1/10 (10%)       1/10 (10%)       0/10 (0%)        0/10 (0%)        3/10 (30%)      | 
|FIRST INCIDENCE    |        93 (T)           93 (T)           93 (T)           ---              ---              93 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.068          P=0.766          P=0.766          P=0.500N         P=0.500N         P=0.293         | 
|POLY 3             |        P=0.065          P=0.760          P=0.760          P=0.500N         P=0.500N         P=0.292         | 
|POLY 1.5           |        P=0.065          P=0.760          P=0.760          P=0.500N         P=0.500N         P=0.292         | 
|POLY 6             |        P=0.065          P=0.760          P=0.760          P=0.500N         P=0.500N         P=0.292         | 
|LOGISTIC REGRESSION|        P=0.068          P=0.766          P=0.766          (e)              (e)              P=0.293         | 
|COCH-ARM / FISHERS |        P=0.066          P=0.763N         P=0.763N         P=0.500N         P=0.500N         P=0.291         | 
|ORDER RESTRICTED   |        P=0.053          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 03                                            Page 5       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 14 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Hemorrhage Focal                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)    | 
|POLY-3 RATE (b)    |        10/10.00         10/10.00         10/10.00         10/10.00         10/10.00         10/10.00        | 
|POLY-3 PERCENT (g) |        100.0%           100.0%           100.0%           100.0%           100.0%           100.0%          | 
|TERMINAL (d)       |        10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)    | 
|FIRST INCIDENCE    |        93 (T)           93 (T)           93 (T)           93 (T)           93 (T)           93 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Hemorrhage Focal                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)    | 
|POLY-3 RATE (b)    |        10/10.00         10/10.00         10/10.00         10/10.00         10/10.00         10/10.00        | 
|POLY-3 PERCENT (g) |        100.0%           100.0%           100.0%           100.0%           100.0%           100.0%          | 
|TERMINAL (d)       |        10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)    | 
|FIRST INCIDENCE    |        93 (T)           93 (T)           93 (T)           93 (T)           93 (T)           93 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 03                                            Page 6       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 14 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolar Epithelium                                                                                                        | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        9/10 (90%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|POLY-3 RATE (b)    |        9/10.00          0/10.00          0/10.00          0/10.00          0/10.00          0/10.00         | 
|POLY-3 PERCENT (g) |        90.0%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        9/10 (90%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.032N*        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 3             |        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 1.5           |        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 6             |        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|LOGISTIC REGRESSION|        P=0.032N*        (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.030N*        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|ORDER RESTRICTED   |        P<0.001N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolar Epithelium                                                                                                        | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        8/10 (80%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|POLY-3 RATE (b)    |        8/10.00          0/10.00          0/10.00          0/10.00          0/10.00          0/10.00         | 
|POLY-3 PERCENT (g) |        80.0%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        8/10 (80%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.045N*        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 3             |        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 1.5           |        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 6             |        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|LOGISTIC REGRESSION|        P=0.045N*        (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.044N*        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|ORDER RESTRICTED   |        P<0.001N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 03                                            Page 7       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 14 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolus                                                                                                                   | 
|     Infiltration Cellular Focal Histiocyte                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        9/10 (90%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|POLY-3 RATE (b)    |        9/10.00          0/10.00          0/10.00          0/10.00          0/10.00          0/10.00         | 
|POLY-3 PERCENT (g) |        90.0%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        9/10 (90%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.032N*        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 3             |        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 1.5           |        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 6             |        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|LOGISTIC REGRESSION|        P=0.032N*        (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.030N*        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|ORDER RESTRICTED   |        P<0.001N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolus                                                                                                                   | 
|     Infiltration Cellular Focal Histiocyte                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        7/10 (70%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)      | 
|POLY-3 RATE (b)    |        7/10.00          0/10.00          0/10.00          0/10.00          0/10.00          1/10.00         | 
|POLY-3 PERCENT (g) |        70.0%            0.0%             0.0%             0.0%             0.0%             10.0%           | 
|TERMINAL (d)       |        7/10 (70%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)      | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              ---              93 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.263N         P=0.003N**       P=0.003N**       P=0.003N**       P=0.003N**       P=0.013N*       | 
|POLY 3             |        P=0.178N         P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P=0.003N**      | 
|POLY 1.5           |        P=0.178N         P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P=0.003N**      | 
|POLY 6             |        P=0.178N         P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P=0.003N**      | 
|LOGISTIC REGRESSION|        P=0.263N         (e)              (e)              (e)              (e)              P=0.013N*       | 
|COCH-ARM / FISHERS |        P=0.261N         P=0.002N**       P=0.002N**       P=0.002N**       P=0.002N**       P=0.010N*       | 
|ORDER RESTRICTED   |        P<0.001N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 03                                            Page 8       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 14 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolus                                                                                                                   | 
|     Inflammation Focal                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        6/10 (60%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|POLY-3 RATE (b)    |        6/10.00          0/10.00          0/10.00          0/10.00          0/10.00          0/10.00         | 
|POLY-3 PERCENT (g) |        60.0%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        6/10 (60%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.091N         P=0.009N**       P=0.009N**       P=0.009N**       P=0.009N**       P=0.009N**      | 
|POLY 3             |        P=0.027N*        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 1.5           |        P=0.027N*        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 6             |        P=0.027N*        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|LOGISTIC REGRESSION|        P=0.091N         (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.089N         P=0.005N**       P=0.005N**       P=0.005N**       P=0.005N**       P=0.005N**      | 
|ORDER RESTRICTED   |        P<0.001N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolus                                                                                                                   | 
|     Inflammation Focal                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/10 (50%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|POLY-3 RATE (b)    |        5/10.00          0/10.00          0/10.00          0/10.00          0/10.00          0/10.00         | 
|POLY-3 PERCENT (g) |        50.0%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        5/10 (50%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.128N         P=0.022N*        P=0.022N*        P=0.022N*        P=0.022N*        P=0.022N*       | 
|POLY 3             |        P=0.071N         P=0.008N**       P=0.008N**       P=0.008N**       P=0.008N**       P=0.008N**      | 
|POLY 1.5           |        P=0.071N         P=0.008N**       P=0.008N**       P=0.008N**       P=0.008N**       P=0.008N**      | 
|POLY 6             |        P=0.071N         P=0.008N**       P=0.008N**       P=0.008N**       P=0.008N**       P=0.008N**      | 
|LOGISTIC REGRESSION|        P=0.128N         (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.126N         P=0.016N*        P=0.016N*        P=0.016N*        P=0.016N*        P=0.016N*       | 
|ORDER RESTRICTED   |        P<0.001N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 03                                            Page 9       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 14 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Peribronchial                                                                                                              | 
|     Hyperplasia Focal Lymphoid                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        6/10 (60%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|POLY-3 RATE (b)    |        6/10.00          0/10.00          0/10.00          0/10.00          0/10.00          0/10.00         | 
|POLY-3 PERCENT (g) |        60.0%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        6/10 (60%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.091N         P=0.009N**       P=0.009N**       P=0.009N**       P=0.009N**       P=0.009N**      | 
|POLY 3             |        P=0.027N*        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 1.5           |        P=0.027N*        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 6             |        P=0.027N*        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|LOGISTIC REGRESSION|        P=0.091N         (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.089N         P=0.005N**       P=0.005N**       P=0.005N**       P=0.005N**       P=0.005N**      | 
|ORDER RESTRICTED   |        P<0.001N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Peribronchial                                                                                                              | 
|     Hyperplasia Focal Lymphoid                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/10 (40%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|POLY-3 RATE (b)    |        4/10.00          0/10.00          0/10.00          0/10.00          0/10.00          0/10.00         | 
|POLY-3 PERCENT (g) |        40.0%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        4/10 (40%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.182N         P=0.051N         P=0.051N         P=0.051N         P=0.051N         P=0.051N        | 
|POLY 3             |        P=0.140N         P=0.033N*        P=0.033N*        P=0.033N*        P=0.033N*        P=0.033N*       | 
|POLY 1.5           |        P=0.140N         P=0.033N*        P=0.033N*        P=0.033N*        P=0.033N*        P=0.033N*       | 
|POLY 6             |        P=0.140N         P=0.033N*        P=0.033N*        P=0.033N*        P=0.033N*        P=0.033N*       | 
|LOGISTIC REGRESSION|        P=0.182N         (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.180N         P=0.043N*        P=0.043N*        P=0.043N*        P=0.043N*        P=0.043N*       | 
|ORDER RESTRICTED   |        P<0.001N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 03                                            Page 10      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 14 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Perivascular                                                                                                               | 
|     Hyperplasia Focal Lymphoid                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        9/10 (90%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|POLY-3 RATE (b)    |        9/10.00          0/10.00          0/10.00          0/10.00          0/10.00          0/10.00         | 
|POLY-3 PERCENT (g) |        90.0%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        9/10 (90%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.032N*        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 3             |        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 1.5           |        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 6             |        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|LOGISTIC REGRESSION|        P=0.032N*        (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.030N*        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|ORDER RESTRICTED   |        P<0.001N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Perivascular                                                                                                               | 
|     Hyperplasia Focal Lymphoid                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        6/10 (60%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|POLY-3 RATE (b)    |        6/10.00          0/10.00          0/10.00          0/10.00          0/10.00          0/10.00         | 
|POLY-3 PERCENT (g) |        60.0%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        6/10 (60%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.091N         P=0.009N**       P=0.009N**       P=0.009N**       P=0.009N**       P=0.009N**      | 
|POLY 3             |        P=0.027N*        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 1.5           |        P=0.027N*        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 6             |        P=0.027N*        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|LOGISTIC REGRESSION|        P=0.091N         (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.089N         P=0.005N**       P=0.005N**       P=0.005N**       P=0.005N**       P=0.005N**      | 
|ORDER RESTRICTED   |        P<0.001N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 03                                            Page 11      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 14 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Bronchial                                                                                                            | 
|     Congestion                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        9/10 (90%)       9/9 (100%)       7/7 (100%)       7/7 (100%)       8/8 (100%)       8/9 (89%)       | 
|POLY-3 RATE (b)    |        9/10.00          9/9.00           7/7.00           7/7.00           8/8.00           8/9.00          | 
|POLY-3 PERCENT (g) |        90.0%            100.0%           100.0%           100.0%           100.0%           88.9%           | 
|TERMINAL (d)       |        9/10 (90%)       9/9 (100%)       7/7 (100%)       7/7 (100%)       8/8 (100%)       8/9 (89%)       | 
|FIRST INCIDENCE    |        93 (T)           93 (T)           93 (T)           93 (T)           93 (T)           93 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.381N         P=0.521          P=0.571          P=0.571          P=0.545          P=0.743N        | 
|POLY 3             |        P=0.383N         P=0.521          P=0.570          P=0.570          P=0.544          P=0.737N        | 
|POLY 1.5           |        P=0.383N         P=0.521          P=0.570          P=0.570          P=0.544          P=0.737N        | 
|POLY 6             |        P=0.383N         P=0.521          P=0.570          P=0.570          P=0.544          P=0.737N        | 
|LOGISTIC REGRESSION|        P=0.381N         P=0.521          P=0.571          P=0.571          P=0.545          P=0.743N        | 
|COCH-ARM / FISHERS |        P=0.379N         P=0.526          P=0.588          P=0.588          P=0.556          P=0.737N        | 
|ORDER RESTRICTED   |        P=0.281N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Bronchial                                                                                                            | 
|     Congestion                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        7/10 (70%)       4/4 (100%)       10/10 (100%)     7/7 (100%)       7/7 (100%)       7/10 (70%)      | 
|POLY-3 RATE (b)    |        7/10.00          4/4.00           10/10.00         7/7.00           7/7.00           7/10.00         | 
|POLY-3 PERCENT (g) |        70.0%            100.0%           100.0%           100.0%           100.0%           70.0%           | 
|TERMINAL (d)       |        7/10 (70%)       4/4 (100%)       10/10 (100%)     7/7 (100%)       7/7 (100%)       7/10 (70%)      | 
|FIRST INCIDENCE    |        93 (T)           93 (T)           93 (T)           93 (T)           93 (T)           93 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.131N         P=0.310          P=0.111          P=0.178          P=0.178          P=0.683         | 
|POLY 3             |        P=0.118N         P=0.307          P=0.095          P=0.166          P=0.166          P=0.678         | 
|POLY 1.5           |        P=0.118N         P=0.307          P=0.095          P=0.166          P=0.166          P=0.678         | 
|POLY 6             |        P=0.118N         P=0.307          P=0.095          P=0.166          P=0.166          P=0.678         | 
|LOGISTIC REGRESSION|        P=0.131N         P=0.310          P=0.111          P=0.178          P=0.178          P=0.683         | 
|COCH-ARM / FISHERS |        P=0.128N         P=0.330          P=0.105          P=0.176          P=0.176          P=0.686N        | 
|ORDER RESTRICTED   |        P=0.060          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 03                                            Page 12      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 14 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Bronchial                                                                                                            | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        8/10 (80%)       0/9 (0%)         0/7 (0%)         0/7 (0%)         0/8 (0%)         0/9 (0%)        | 
|POLY-3 RATE (b)    |        8/10.00          0/9.00           0/7.00           0/7.00           0/8.00           0/9.00          | 
|POLY-3 PERCENT (g) |        80.0%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        8/10 (80%)       0/9 (0%)         0/7 (0%)         0/7 (0%)         0/8 (0%)         0/9 (0%)        | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.042N*        P<0.001N**       P=0.004N**       P=0.004N**       P=0.002N**       P<0.001N**      | 
|POLY 3             |        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 1.5           |        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 6             |        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**      | 
|LOGISTIC REGRESSION|        P=0.042N*        (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.040N*        P<0.001N**       P=0.002N**       P=0.002N**       P<0.001N**       P<0.001N**      | 
|ORDER RESTRICTED   |        P<0.001N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Bronchial                                                                                                            | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/10 (40%)       0/4 (0%)         0/10 (0%)        0/7 (0%)         0/7 (0%)         0/10 (0%)       | 
|POLY-3 RATE (b)    |        4/10.00          0/4.00           0/10.00          0/7.00           0/7.00           0/10.00         | 
|POLY-3 PERCENT (g) |        40.0%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        4/10 (40%)       0/4 (0%)         0/10 (0%)        0/7 (0%)         0/7 (0%)         0/10 (0%)       | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.153N         P=0.209N         P=0.051N         P=0.098N         P=0.098N         P=0.051N        | 
|POLY 3             |        P=0.116N         P=0.198N         P=0.033N*        P=0.079N         P=0.079N         P=0.033N*       | 
|POLY 1.5           |        P=0.116N         P=0.198N         P=0.033N*        P=0.079N         P=0.079N         P=0.033N*       | 
|POLY 6             |        P=0.116N         P=0.198N         P=0.033N*        P=0.079N         P=0.079N         P=0.033N*       | 
|LOGISTIC REGRESSION|        P=0.153N         (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.151N         P=0.210N         P=0.043N*        P=0.088N         P=0.088N         P=0.043N*       | 
|ORDER RESTRICTED   |        P<0.001N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 03                                            Page 13      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 14 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mediastinal                                                                                                          | 
|     Congestion                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        8/10 (80%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         9/9 (100%)      | 
|POLY-3 RATE (b)    |        8/10.00          0/0.00           0/0.00           0/0.00           0/0.00           9/9.00          | 
|POLY-3 PERCENT (g) |        80.0%            0.0%             0.0%             0.0%             0.0%             100.0%          | 
|TERMINAL (d)       |        8/10 (80%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         9/9 (100%)      | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              ---              93 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.189          P=1.000          P=1.000N         P=1.000N         P=1.000          P=0.257         | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              P=0.251         | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              P=0.251         | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              P=0.251         | 
|LOGISTIC REGRESSION|        P=0.189          (e)              (e)              (e)              (e)              P=0.257         | 
|COCH-ARM / FISHERS |        P=0.183          P=1.000          P=1.000          P=1.000          P=1.000          P=0.263         | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mediastinal                                                                                                          | 
|     Congestion                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        8/9 (89%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         8/10 (80%)      | 
|POLY-3 RATE (b)    |        8/9.00           0/0.00           0/0.00           0/0.00           0/0.00           8/10.00         | 
|POLY-3 PERCENT (g) |        88.9%            0.0%             0.0%             0.0%             0.0%             80.0%           | 
|TERMINAL (d)       |        8/9 (89%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         8/10 (80%)      | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              ---              93 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.462N         P=1.000N         P=1.000N         P=1.000          P=1.000          P=0.539N        | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              P=0.538N        | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              P=0.538N        | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              P=0.538N        | 
|LOGISTIC REGRESSION|        P=0.462N         (e)              (e)              (e)              (e)              P=0.539N        | 
|COCH-ARM / FISHERS |        P=0.461N         P=1.000          P=1.000          P=1.000          P=1.000          P=0.542N        | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 03                                            Page 14      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 14 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mediastinal                                                                                                          | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        9/10 (90%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         1/9 (11%)       | 
|POLY-3 RATE (b)    |        9/10.00          0/0.00           0/0.00           0/0.00           0/0.00           1/9.00          | 
|POLY-3 PERCENT (g) |        90.0%            0.0%             0.0%             0.0%             0.0%             11.1%           | 
|TERMINAL (d)       |        9/10 (90%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         1/9 (11%)       | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              ---              93 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001N**       P=1.000N         P=1.000N         P=1.000N         P=1.000N         P=0.002N**      | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              P<0.001N**      | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              P<0.001N**      | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              P<0.001N**      | 
|LOGISTIC REGRESSION|        P<0.001N**       (e)              (e)              (e)              (e)              P=0.002N**      | 
|COCH-ARM / FISHERS |        P<0.001N**       P=1.000          P=1.000          P=1.000          P=1.000          P<0.001N**      | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mediastinal                                                                                                          | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        7/9 (78%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         4/10 (40%)      | 
|POLY-3 RATE (b)    |        7/9.00           0/0.00           0/0.00           0/0.00           0/0.00           4/10.00         | 
|POLY-3 PERCENT (g) |        77.8%            0.0%             0.0%             0.0%             0.0%             40.0%           | 
|TERMINAL (d)       |        7/9 (78%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         4/10 (40%)      | 
|FIRST INCIDENCE    |        93 (T)           ---              ---              ---              ---              93 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.095N         P=1.000          P=1.000          P=1.000          P=1.000          P=0.121N        | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              P=0.110N        | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              P=0.110N        | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              P=0.110N        | 
|LOGISTIC REGRESSION|        P=0.095N         (e)              (e)              (e)              (e)              P=0.121N        | 
|COCH-ARM / FISHERS |        P=0.089N         P=1.000          P=1.000          P=1.000          P=1.000          P=0.115N        | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 03                                            Page 15      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 14 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary: Periovarian Tissue                                                                                                        | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                                                                                                             | 
|POLY-3 RATE (b)    |                                                                                                             | 
|POLY-3 PERCENT (g) |                                                                                                             | 
|TERMINAL (d)       |                                                                                                             | 
|FIRST INCIDENCE    |                                                                                                             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                                                                                                             | 
|POLY 3             |                                                                                                             | 
|POLY 1.5           |                                                                                                             | 
|POLY 6             |                                                                                                             | 
|LOGISTIC REGRESSION|                                                                                                             | 
|COCH-ARM / FISHERS |                                                                                                             | 
|ORDER RESTRICTED   |                                                                                                             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary: Periovarian Tissue                                                                                                        | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/10 (20%)       0/0 (0%)         2/3 (67%)        0/0 (0%)         0/0 (0%)         0/10 (0%)       | 
|POLY-3 RATE (b)    |        2/10.00          0/0.00           2/3.00           0/0.00           0/0.00           0/10.00         | 
|POLY-3 PERCENT (g) |        20.0%            0.0%             66.7%            0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        2/10 (20%)       0/0 (0%)         2/3 (67%)        0/0 (0%)         0/0 (0%)         0/10 (0%)       | 
|FIRST INCIDENCE    |        93 (T)           ---              93 (T)           ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.070N         P=1.000          P=0.215          P=1.000          P=1.000          P=0.234N        | 
|POLY 3             |        (e)              (e)              P=0.201          (e)              (e)              P=0.227N        | 
|POLY 1.5           |        (e)              (e)              P=0.201          (e)              (e)              P=0.227N        | 
|POLY 6             |        (e)              (e)              P=0.201          (e)              (e)              P=0.227N        | 
|LOGISTIC REGRESSION|        P=0.070N         (e)              P=0.215          (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.066N         P=1.000          P=0.203          P=1.000          P=1.000          P=0.237N        | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 03                                            Page 16      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 14 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas                                                                                                                         | 
|     Accessory Spleen                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/10 (0%)        0/0 (0%)         0/0 (0%)         1/1 (100%)       2/3 (67%)        0/10 (0%)       | 
|POLY-3 RATE (b)    |        0/10.00          0/0.00           0/0.00           1/1.00           2/3.00           0/10.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             100.0%           66.7%            0.0%            | 
|TERMINAL (d)       |        0/10 (0%)        0/0 (0%)         0/0 (0%)         1/1 (100%)       2/3 (67%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              93 (T)           93 (T)           ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.345N         (e)              (e)              P=0.077          P=0.034 *        (e)             | 
|POLY 3             |        (e)              (e)              (e)              P=0.091N         P=0.003 **       (e)             | 
|POLY 1.5           |        (e)              (e)              (e)              P=0.091N         P=0.003 **       (e)             | 
|POLY 6             |        (e)              (e)              (e)              P=0.091N         P=0.003 **       (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.077          P=0.034 *        (e)             | 
|COCH-ARM / FISHERS |        P=0.341N         (e)              (e)              P=0.091          P=0.038 *        (e)             | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas                                                                                                                         | 
|     Accessory Spleen                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/10 (0%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/10 (0%)       | 
|POLY-3 RATE (b)    |        0/10.00          0/0.00           0/0.00           0/0.00           0/0.00           0/10.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/10 (0%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/10 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|ORDER RESTRICTED   |        (e)              (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).