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TDMS Study 05135-05 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Northwest                                         ISOPRENE                                       DATE: 10/15/04       
EXPERIMENT: 05135 TEST: 05                                                                                     TIME: 13:17:12       
TEST TYPE:  SIX MONTH EXPOS.                                                                                   PAGE:       1        
CONT: N01-ES-55105                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: 61825C       
PATHOLOGIST: HAILEY, JAMES R.                PERSING, RONALD                                                   CAS: 78-79-5         
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
                                                                                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Northwest                                         ISOPRENE                                       DATE: 10/15/04       
EXPERIMENT: 05135 TEST: 05                                                                                     TIME: 13:17:12       
TEST TYPE:  SIX MONTH EXPOS.                                                                                                        
CONT: N01-ES-55105                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: 61825C       
PATHOLOGIST: HAILEY, JAMES R.                PERSING, RONALD                                                   CAS: 78-79-5         
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF                        ISOPRENE                                                                                  
===============================================================                                                                     
Male Rats                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Heart                                  Cardiomyopathy                                                                               
                                       Cardiomyopathy Focal                                                                         
Kidney                                 Nephropathy Chronic                                                                          
Kidney: Bilateral                      Nephropathy Chronic                                                                          
Larynx                                 Infiltration Cellular Mixed Cell                                                             
Liver                                  Fatty Change                                                                                 
                                       Fatty Change Focal                                                                           
                                       Hepatodiaphragmatic Nodule                                                                   
                                       Necrosis Focal                                                                               
Lung                                   Hemorrhage Focal                                                                             
Lung: Alveolar Epithelium              Hyperplasia                                                                                  
                                       Hyperplasia Focal                                                                            
Lung: Alveolus                         Hemorrhage                                                                                   
                                       Infiltration Cellular Focal Histiocyte                                                       
                                       Infiltration Cellular Histiocyte                                                             
Lung: Peribronchial                    Hyperplasia Focal Lymphoid                                                                   
                                       Hyperplasia Lymphoid Focal                                                                   
Lung: Perivascular                     Hyperplasia Lymphoid Focal                                                                   
Lymph Node, Bronchial                  Congestion                                                                                   
                                       Hyperplasia                                                                                  
Lymph Node, Mandibular                 Hyperplasia                                                                                  
Lymph Node, Mediastinal                Congestion                                                                                   
                                       Hyperplasia                                                                                  
                                       Pigmentation Hemosiderin                                                                     
Mammary Gland                          Hyperplasia                                                                                  
Mesentery                              Necrosis                                                                                     
Pituitary Gland                        Hyperplasia                                                                                  
Preputial Gland                        Infiltration Cellular Mixed Cell                                                             
                                       Inflammation                                                                                 
Prostate                               Inflammation                                                                                 
Spleen                                 Accessory Spleen                                                                             
Testes: Interstitial Cell              Hyperplasia                                                                                  
Urinary Bladder                        Calculus Micro Observation Only                                                              
===============================================================                                                                     
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 1       
                     Statistical Analysis of Non-neoplastic Lesions in        Rats(FISCHER 344)  -                         ISOPRENE 
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/5 (80%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         3/6 (50%)       | 
|POLY-3 RATE (b)    |        4/5.00           0/0.00           0/0.00           0/0.00           0/0.00           3/4.26          | 
|POLY-3 PERCENT (g) |        80.0%            0.0%             0.0%             0.0%             0.0%             70.4%           | 
|INT SACRIFICE 1 (c)|        2/2 (100%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/2 (0%)        | 
|TERMINAL (d)       |        2/3 (67%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         3/4 (75%)       | 
|FIRST INCIDENCE    |        186 (I)          ---              ---              ---              ---              366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.275N         P=1.000          P=1.000          P=1.000          P=1.000          P=0.339N        | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              P=0.655N        | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              P=0.555N        | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              P=0.704N        | 
|LOGISTIC REGRESSION|        P=0.253N         (e)              (e)              (e)              (e)              P=0.322N        | 
|COCH-ARM / FISHERS |        P=0.275N         P=1.000          P=1.000          P=1.000          P=1.000          P=0.348N        | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Hyperplasia Lymphoid Focal                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/5 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         3/6 (50%)       | 
|POLY-3 RATE (b)    |        0/3.26           0/0.00           0/0.00           0/0.00           0/0.00           3/6.00          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             50.0%           | 
|INT SACRIFICE 1 (c)|        0/2 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         2/2 (100%)      | 
|TERMINAL (d)       |        0/3 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         1/4 (25%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.077          (e)              (e)              (e)              (e)              P=0.111         | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              P=0.216         | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              P=0.174         | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              P=0.241         | 
|LOGISTIC REGRESSION|        P=0.055          (e)              (e)              (e)              (e)              P=0.085         | 
|COCH-ARM / FISHERS |        P=0.083          (e)              (e)              (e)              (e)              P=0.121         | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 2       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart                                                                                                                            | 
|     Cardiomyopathy                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        0/10 (0%)        0/11 (0%)        0/10 (0%)        0/10 (0%)        12/40 (30%)     | 
|POLY-3 RATE (b)    |        1/31.31          0/1.31           0/1.40           0/1.31           0/1.31           12/33.92        | 
|POLY-3 PERCENT (g) |        3.2%             0.0%             0.0%             0.0%             0.0%             35.4%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        3/10 (30%)      | 
|TERMINAL (d)       |        1/30 (3%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         9/30 (30%)      | 
|FIRST INCIDENCE    |        366 (T)          ---              ---              ---              ---              186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=1.000N         P=1.000N         P=1.000N         P=1.000N         P<0.001 **      | 
|POLY 3             |        P<0.001 **       P=0.856N         P=0.846N         P=0.856N         P=0.856N         P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       P=0.834N         P=0.822N         P=0.834N         P=0.834N         P<0.001 **      | 
|POLY 6             |        P<0.001 **       P=0.866N         P=0.857N         P=0.866N         P=0.866N         P<0.001 **      | 
|LOGISTIC REGRESSION|        P<0.001 **       (e)              (e)              (e)              (e)              P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.800N         P=0.784N         P=0.800N         P=0.800N         P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart                                                                                                                            | 
|     Cardiomyopathy Focal                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        16/40 (40%)      0/10 (0%)        0/11 (0%)        0/10 (0%)        0/10 (0%)        2/40 (5%)       | 
|POLY-3 RATE (b)    |        16/37.39         0/1.31           0/1.40           0/1.31           0/1.31           2/32.18         | 
|POLY-3 PERCENT (g) |        42.8%            0.0%             0.0%             0.0%             0.0%             6.2%            | 
|INT SACRIFICE 1 (c)|        7/10 (70%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)      | 
|TERMINAL (d)       |        9/30 (30%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         1/30 (3%)       | 
|FIRST INCIDENCE    |        186 (I)          ---              ---              ---              ---              186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.004N**       P=0.003N**       P=0.003N**       P=0.003N**       P=0.003N**       P<0.001N**      | 
|POLY 3             |        P<0.001N**       P=0.487N         P=0.478N         P=0.487N         P=0.487N         P<0.001N**      | 
|POLY 1.5           |        P<0.001N**       P=0.244N         P=0.227N         P=0.244N         P=0.244N         P<0.001N**      | 
|POLY 6             |        P<0.001N**       P=0.622N         P=0.617N         P=0.622N         P=0.622N         P<0.001N**      | 
|LOGISTIC REGRESSION|        P=0.004N**       P=0.002N**       P=0.002N**       P=0.002N**       P=0.002N**       P<0.001N**      | 
|COCH-ARM / FISHERS |        P=0.008N**       P=0.013N*        P=0.009N**       P=0.013N*        P=0.013N*        P<0.001N**      | 
|ORDER RESTRICTED   |        P<0.001N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 3       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Islets, Pancreatic                                                                                                               | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/40 (10%)       0/10 (0%)        0/11 (0%)        0/10 (0%)        0/10 (0%)        6/40 (15%)      | 
|POLY-3 RATE (b)    |        4/31.31          0/1.31           0/1.40           0/1.31           0/1.31           6/31.31         | 
|POLY-3 PERCENT (g) |        12.8%            0.0%             0.0%             0.0%             0.0%             19.2%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        4/30 (13%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         6/30 (20%)      | 
|FIRST INCIDENCE    |        366 (T)          ---              ---              ---              ---              366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.326          P=1.000          P=1.000          P=1.000          P=1.000          P=0.366         | 
|POLY 3             |        P=0.257          P=0.661N         P=0.651N         P=0.661N         P=0.661N         P=0.366         | 
|POLY 1.5           |        P=0.203          P=0.556N         P=0.540N         P=0.556N         P=0.556N         P=0.366         | 
|POLY 6             |        P=0.266          P=0.714N         P=0.706N         P=0.714N         P=0.714N         P=0.366         | 
|LOGISTIC REGRESSION|        P=0.326          (e)              (e)              (e)              (e)              P=0.366         | 
|COCH-ARM / FISHERS |        P=0.075          P=0.397N         P=0.366N         P=0.397N         P=0.397N         P=0.369         | 
|ORDER RESTRICTED   |        P=0.100          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy Chronic                                                                                                         | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        23/40 (57%)      0/10 (0%)        1/12 (8%)        2/12 (17%)       6/16 (38%)       29/40 (73%)     | 
|POLY-3 RATE (b)    |        23/31.31         0/1.31           1/2.40           2/3.31           6/7.31           29/31.31        | 
|POLY-3 PERCENT (g) |        73.5%            0.0%             41.7%            60.4%            82.1%            92.6%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        23/30 (77%)      0/0 (0%)         1/1 (100%)       2/2 (100%)       6/6 (100%)       29/30 (97%)     | 
|FIRST INCIDENCE    |        366 (T)          ---              366 (T)          366 (T)          366 (T)          366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.031 *        P=1.000          P=0.744          P=0.543          P=0.229          P=0.030 *       | 
|POLY 3             |        P=0.004 **       P=0.341N         P=0.424N         P=0.540N         P=0.497          P=0.029 *       | 
|POLY 1.5           |        P<0.001 **       P=0.052N         P=0.086N         P=0.174N         P=0.515N         P=0.046 *       | 
|POLY 6             |        P=0.006 **       P=0.637N         P=0.643          P=0.566          P=0.304          P=0.026 *       | 
|LOGISTIC REGRESSION|        P=0.030 *        (e)              P=0.744          P=0.543          P=0.229          P=0.030 *       | 
|COCH-ARM / FISHERS |        P<0.001 **       P<0.001N**       P=0.003N**       P=0.014N*        P=0.145N         P=0.120         | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 4       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Bilateral                                                                                                                | 
|     Nephropathy Chronic                                                                                                         | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        23/40 (57%)      0/10 (0%)        1/12 (8%)        1/12 (8%)        6/16 (38%)       29/40 (73%)     | 
|POLY-3 RATE (b)    |        23/31.31         0/1.31           1/2.40           1/3.31           6/7.31           29/31.31        | 
|POLY-3 PERCENT (g) |        73.5%            0.0%             41.7%            30.2%            82.1%            92.6%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        23/30 (77%)      0/0 (0%)         1/1 (100%)       1/2 (50%)        6/6 (100%)       29/30 (97%)     | 
|FIRST INCIDENCE    |        366 (T)          ---              366 (T)          366 (T)          366 (T)          366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.020 *        P=1.000          P=0.744          P=0.500N         P=0.229          P=0.030 *       | 
|POLY 3             |        P=0.003 **       P=0.341N         P=0.424N         P=0.237N         P=0.497          P=0.029 *       | 
|POLY 1.5           |        P<0.001 **       P=0.052N         P=0.086N         P=0.047N*        P=0.515N         P=0.046 *       | 
|POLY 6             |        P=0.006 **       P=0.637N         P=0.643          P=0.460N         P=0.304          P=0.026 *       | 
|LOGISTIC REGRESSION|        P=0.020 *        (e)              P=0.744          P=0.500N         P=0.229          P=0.030 *       | 
|COCH-ARM / FISHERS |        P<0.001 **       P<0.001N**       P=0.003N**       P=0.003N**       P=0.145N         P=0.120         | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Larynx                                                                                                                           | 
|     Infiltration Cellular Mixed Cell                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        3/40 (8%)       | 
|POLY-3 RATE (b)    |        1/31.31          0/1.31           0/1.31           0/1.31           0/1.31           3/31.31         | 
|POLY-3 PERCENT (g) |        3.2%             0.0%             0.0%             0.0%             0.0%             9.6%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        1/30 (3%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         3/30 (10%)      | 
|FIRST INCIDENCE    |        366 (T)          ---              ---              ---              ---              366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.250          P=1.000          P=1.000          P=1.000N         P=1.000          P=0.304         | 
|POLY 3             |        P=0.175          P=0.856N         P=0.856N         P=0.856N         P=0.856N         P=0.303         | 
|POLY 1.5           |        P=0.158          P=0.834N         P=0.834N         P=0.834N         P=0.834N         P=0.304         | 
|POLY 6             |        P=0.176          P=0.866N         P=0.866N         P=0.866N         P=0.866N         P=0.303         | 
|LOGISTIC REGRESSION|        P=0.250          (e)              (e)              (e)              (e)              P=0.304         | 
|COCH-ARM / FISHERS |        P=0.094          P=0.800N         P=0.800N         P=0.800N         P=0.800N         P=0.308         | 
|ORDER RESTRICTED   |        P=0.041 *        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 5       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Fatty Change                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        0/15 (0%)        3/22 (14%)       4/15 (27%)       0/17 (0%)        0/40 (0%)       | 
|POLY-3 RATE (b)    |        1/31.31          0/6.31           3/12.40          4/6.31           0/8.31           0/31.31         | 
|POLY-3 PERCENT (g) |        3.2%             0.0%             24.2%            63.4%            0.0%             0.0%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        1/30 (3%)        0/5 (0%)         3/11 (27%)       4/5 (80%)        0/7 (0%)         0/30 (0%)       | 
|FIRST INCIDENCE    |        366 (T)          ---              366 (T)          366 (T)          ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.040N*        P=0.846N         P=0.047 *        P<0.001 **       P=0.786N         P=0.500N        | 
|POLY 3             |        P=0.062N         P=0.765N         P=0.065          P<0.001 **       P=0.733N         P=0.500N        | 
|POLY 1.5           |        P=0.057N         P=0.744N         P=0.080          P=0.002 **       P=0.713N         P=0.500N        | 
|POLY 6             |        P=0.068N         P=0.777N         P=0.058          P<0.001 **       P=0.743N         P=0.500N        | 
|LOGISTIC REGRESSION|        P=0.040N*        (e)              P=0.047 *        P<0.001 **       (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.069N         P=0.727N         P=0.124          P=0.017 *        P=0.702N         P=0.500N        | 
|ORDER RESTRICTED   |        P=0.002N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Fatty Change Focal                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        0/15 (0%)        2/22 (9%)        1/15 (7%)        1/17 (6%)        0/40 (0%)       | 
|POLY-3 RATE (b)    |        0/31.31          0/6.31           2/12.40          1/6.31           1/8.31           0/31.31         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             16.1%            15.8%            12.0%            0.0%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/30 (0%)        0/5 (0%)         2/11 (18%)       1/5 (20%)        1/7 (14%)        0/30 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              366 (T)          366 (T)          366 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.223N         (e)              P=0.060          P=0.154          P=0.214          (e)             | 
|POLY 3             |        P=0.289N         (e)              P=0.076          P=0.227          P=0.262          (e)             | 
|POLY 1.5           |        P=0.282N         (e)              P=0.087          P=0.250          P=0.283          (e)             | 
|POLY 6             |        P=0.298N         (e)              P=0.071          P=0.215          P=0.251          (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              P=0.060          P=0.154          P=0.214          (e)             | 
|COCH-ARM / FISHERS |        P=0.290N         (e)              P=0.122          P=0.273          P=0.298          (e)             | 
|ORDER RESTRICTED   |        P=0.039 *        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 6       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatodiaphragmatic Nodule                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/40 (13%)       9/15 (60%)       8/22 (36%)       4/15 (27%)       8/17 (47%)       6/40 (15%)      | 
|POLY-3 RATE (b)    |        5/33.92          9/9.79           8/13.27          4/8.92           8/10.92          6/31.31         | 
|POLY-3 PERCENT (g) |        14.7%            92.0%            60.3%            44.9%            73.3%            19.2%           | 
|INT SACRIFICE 1 (c)|        3/10 (30%)       4/10 (40%)       1/10 (10%)       3/10 (30%)       3/10 (30%)       0/10 (0%)       | 
|TERMINAL (d)       |        2/30 (7%)        5/5 (100%)       7/11 (64%)       1/5 (20%)        5/7 (71%)        6/30 (20%)      | 
|FIRST INCIDENCE    |        186 (I)          186 (I)          186 (I)          186 (I)          186 (I)          366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.059N         P=0.002 **       P=0.020 *        P=0.476          P=0.012 *        P=0.500         | 
|POLY 3             |        P=0.053N         P<0.001 **       P=0.003 **       P=0.084          P<0.001 **       P=0.443         | 
|POLY 1.5           |        P=0.054N         P<0.001 **       P=0.006 **       P=0.112          P<0.001 **       P=0.460         | 
|POLY 6             |        P=0.056N         P<0.001 **       P=0.002 **       P=0.071          P<0.001 **       P=0.433         | 
|LOGISTIC REGRESSION|        P=0.060N         P=0.002 **       P=0.021 *        P=0.476          P=0.011 *        P=0.500         | 
|COCH-ARM / FISHERS |        P=0.081N         P<0.001 **       P=0.032 *        P=0.193          P=0.008 **       P=0.500         | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation Focal                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/40 (5%)        0/15 (0%)        0/22 (0%)        0/15 (0%)        0/17 (0%)        1/40 (3%)       | 
|POLY-3 RATE (b)    |        2/31.31          0/6.31           0/12.40          0/6.31           0/8.31           1/32.18         | 
|POLY-3 PERCENT (g) |        6.4%             0.0%             0.0%             0.0%             0.0%             3.1%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)      | 
|TERMINAL (d)       |        2/30 (7%)        0/5 (0%)         0/11 (0%)        0/5 (0%)         0/7 (0%)         0/30 (0%)       | 
|FIRST INCIDENCE    |        366 (T)          ---              ---              ---              ---              186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.677          P=0.670N         P=0.476N         P=0.670N         P=0.588N         P=0.500N        | 
|POLY 3             |        P=0.560N         P=0.602N         P=0.460N         P=0.602N         P=0.549N         P=0.490N        | 
|POLY 1.5           |        P=0.612N         P=0.558N         P=0.432N         P=0.558N         P=0.512N         P=0.493N        | 
|POLY 6             |        P=0.529N         P=0.626N         P=0.476N         P=0.626N         P=0.570N         P=0.489N        | 
|LOGISTIC REGRESSION|        P=0.677          (e)              (e)              (e)              (e)              P=0.500N        | 
|COCH-ARM / FISHERS |        P=0.662          P=0.525N         P=0.412N         P=0.525N         P=0.489N         P=0.500N        | 
|ORDER RESTRICTED   |        P=0.095N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 7       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Necrosis Focal                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        0/15 (0%)        3/22 (14%)       0/15 (0%)        0/17 (0%)        4/40 (10%)      | 
|POLY-3 RATE (b)    |        1/31.31          0/6.31           3/12.40          0/6.31           0/8.31           4/31.31         | 
|POLY-3 PERCENT (g) |        3.2%             0.0%             24.2%            0.0%             0.0%             12.8%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        1/30 (3%)        0/5 (0%)         3/11 (27%)       0/5 (0%)         0/7 (0%)         4/30 (13%)      | 
|FIRST INCIDENCE    |        366 (T)          ---              366 (T)          ---              ---              366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.274          P=0.846N         P=0.047 *        P=0.846N         P=0.786N         P=0.177         | 
|POLY 3             |        P=0.209          P=0.765N         P=0.065          P=0.765N         P=0.733N         P=0.175         | 
|POLY 1.5           |        P=0.190          P=0.744N         P=0.080          P=0.744N         P=0.713N         P=0.176         | 
|POLY 6             |        P=0.219          P=0.777N         P=0.058          P=0.777N         P=0.743N         P=0.175         | 
|LOGISTIC REGRESSION|        P=0.274          (e)              P=0.047 *        (e)              (e)              P=0.177         | 
|COCH-ARM / FISHERS |        P=0.153          P=0.727N         P=0.124          P=0.727N         P=0.702N         P=0.179         | 
|ORDER RESTRICTED   |        P=0.029 *        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/40 (13%)       10/40 (25%)      11/40 (28%)      10/40 (25%)      10/40 (25%)      5/40 (13%)      | 
|POLY-3 RATE (b)    |        5/31.31          10/40.00         11/39.09         10/40.00         10/40.00         5/32.18         | 
|POLY-3 PERCENT (g) |        16.0%            25.0%            28.1%            25.0%            25.0%            15.5%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     1/10 (10%)      | 
|TERMINAL (d)       |        5/30 (17%)       0/30 (0%)        1/29 (3%)        0/30 (0%)        0/30 (0%)        4/30 (13%)      | 
|FIRST INCIDENCE    |        366 (T)          186 (I)          186 (I)          186 (I)          186 (I)          186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.074N         P=0.102          P=0.060          P=0.102          P=0.102          P=0.632         | 
|POLY 3             |        P=0.224N         P=0.267          P=0.181          P=0.267          P=0.267          P=0.616N        | 
|POLY 1.5           |        P=0.196N         P=0.218          P=0.144          P=0.218          P=0.218          P=0.621N        | 
|POLY 6             |        P=0.240N         P=0.293          P=0.203          P=0.293          P=0.293          P=0.613N        | 
|LOGISTIC REGRESSION|        P=0.089N         P=0.098          P=0.081          P=0.098          P=0.098          P=0.633N        | 
|COCH-ARM / FISHERS |        P=0.139N         P=0.126          P=0.081          P=0.126          P=0.126          P=0.631N        | 
|ORDER RESTRICTED   |        P=0.412N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 8       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Hemorrhage Focal                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        35/40 (88%)      30/40 (75%)      26/40 (65%)      24/40 (60%)      22/40 (55%)      35/40 (88%)     | 
|POLY-3 RATE (b)    |        35/40.00         30/31.31         26/30.40         24/31.31         22/31.31         35/39.13        | 
|POLY-3 PERCENT (g) |        87.5%            95.8%            85.5%            76.7%            70.3%            89.4%           | 
|INT SACRIFICE 1 (c)|        10/10 (100%)     0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        9/10 (90%)      | 
|TERMINAL (d)       |        25/30 (83%)      30/30 (100%)     26/29 (90%)      24/30 (80%)      22/30 (73%)      26/30 (87%)     | 
|FIRST INCIDENCE    |        186 (I)          366 (T)          366 (T)          366 (T)          366 (T)          186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.067          P=0.102N         P=0.021N*        P=0.004N**       P<0.001N**       P=0.632         | 
|POLY 3             |        P=0.474          P=0.193          P=0.546N         P=0.182N         P=0.061N         P=0.532         | 
|POLY 1.5           |        P=0.284          P=0.560          P=0.236N         P=0.062N         P=0.017N*        P=0.560         | 
|POLY 6             |        P=0.583          P=0.075          P=0.567          P=0.288N         P=0.110N         P=0.518         | 
|LOGISTIC REGRESSION|        P=0.063          P=0.098N         P=0.015N*        P=0.004N**       P<0.001N**       P=0.633         | 
|COCH-ARM / FISHERS |        P=0.088          P=0.126N         P=0.017N*        P=0.005N**       P<0.001N**       P=0.631N        | 
|ORDER RESTRICTED   |        P=0.075N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolar Epithelium                                                                                                        | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        3/40 (8%)        0/40 (0%)        0/40 (0%)        1/40 (3%)        0/40 (0%)        1/40 (3%)       | 
|POLY-3 RATE (b)    |        3/31.31          0/31.31          0/30.40          1/31.31          0/31.31          1/32.18         | 
|POLY-3 PERCENT (g) |        9.6%             0.0%             0.0%             3.2%             0.0%             3.1%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)      | 
|TERMINAL (d)       |        3/30 (10%)       0/30 (0%)        0/29 (0%)        1/30 (3%)        0/30 (0%)        0/30 (0%)       | 
|FIRST INCIDENCE    |        366 (T)          ---              ---              366 (T)          ---              186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.612N         P=0.120N         P=0.126N         P=0.304N         P=0.120N         P=0.306N        | 
|POLY 3             |        P=0.607N         P=0.116N         P=0.122N         P=0.303N         P=0.116N         P=0.294N        | 
|POLY 1.5           |        P=0.610N         P=0.117N         P=0.120N         P=0.304N         P=0.117N         P=0.297N        | 
|POLY 6             |        P=0.605N         P=0.116N         P=0.122N         P=0.303N         P=0.116N         P=0.292N        | 
|LOGISTIC REGRESSION|        P=0.614N         (e)              (e)              P=0.304N         (e)              P=0.304N        | 
|COCH-ARM / FISHERS |        P=0.615N         P=0.120N         P=0.120N         P=0.308N         P=0.120N         P=0.308N        | 
|ORDER RESTRICTED   |        P=0.026N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 9       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolar Epithelium                                                                                                        | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/40 (5%)        15/40 (38%)      13/40 (33%)      11/40 (28%)      12/40 (30%)      5/40 (13%)      | 
|POLY-3 RATE (b)    |        2/31.31          15/31.31         13/30.40         11/31.31         12/31.31         5/31.31         | 
|POLY-3 PERCENT (g) |        6.4%             47.9%            42.8%            35.1%            38.3%            16.0%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        2/30 (7%)        15/30 (50%)      13/29 (45%)      11/30 (37%)      12/30 (40%)      5/30 (17%)      | 
|FIRST INCIDENCE    |        366 (T)          366 (T)          366 (T)          366 (T)          366 (T)          366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.066N         P<0.001 **       P<0.001 **       P=0.006 **       P=0.003 **       P=0.213         | 
|POLY 3             |        P=0.061N         P<0.001 **       P<0.001 **       P=0.005 **       P=0.002 **       P=0.212         | 
|POLY 1.5           |        P=0.064N         P<0.001 **       P<0.001 **       P=0.005 **       P=0.002 **       P=0.212         | 
|POLY 6             |        P=0.060N         P<0.001 **       P<0.001 **       P=0.005 **       P=0.002 **       P=0.211         | 
|LOGISTIC REGRESSION|        P=0.066N         P<0.001 **       P<0.001 **       P=0.006 **       P=0.003 **       P=0.213         | 
|COCH-ARM / FISHERS |        P=0.081N         P<0.001 **       P=0.002 **       P=0.006 **       P=0.003 **       P=0.216         | 
|ORDER RESTRICTED   |        P=0.006 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolus                                                                                                                   | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/40 (5%)        0/40 (0%)        0/40 (0%)        0/40 (0%)        1/40 (3%)        3/40 (8%)       | 
|POLY-3 RATE (b)    |        2/31.31          0/31.31          0/30.40          0/31.31          1/31.31          3/32.18         | 
|POLY-3 PERCENT (g) |        6.4%             0.0%             0.0%             0.0%             3.2%             9.3%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)      | 
|TERMINAL (d)       |        2/30 (7%)        0/30 (0%)        0/29 (0%)        0/30 (0%)        1/30 (3%)        2/30 (7%)       | 
|FIRST INCIDENCE    |        366 (T)          ---              ---              ---              366 (T)          186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.040 *        P=0.238N         P=0.245N         P=0.238N         P=0.500N         P=0.500         | 
|POLY 3             |        P=0.041 *        P=0.236N         P=0.243N         P=0.236N         P=0.500N         P=0.513         | 
|POLY 1.5           |        P=0.040 *        P=0.236N         P=0.241N         P=0.236N         P=0.500N         P=0.509         | 
|POLY 6             |        P=0.041 *        P=0.236N         P=0.243N         P=0.236N         P=0.500N         P=0.515         | 
|LOGISTIC REGRESSION|        P=0.039 *        (e)              (e)              (e)              P=0.500N         P=0.500         | 
|COCH-ARM / FISHERS |        P=0.039 *        P=0.247N         P=0.247N         P=0.247N         P=0.500N         P=0.500         | 
|ORDER RESTRICTED   |        P=0.058          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 10      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolus                                                                                                                   | 
|     Infiltration Cellular Focal Histiocyte                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/40 (10%)       17/40 (43%)      19/40 (48%)      17/40 (43%)      16/40 (40%)      19/40 (48%)     | 
|POLY-3 RATE (b)    |        4/33.05          17/31.31         19/30.40         17/31.31         16/31.31         19/31.31        | 
|POLY-3 PERCENT (g) |        12.1%            54.3%            62.5%            54.3%            51.1%            60.7%           | 
|INT SACRIFICE 1 (c)|        2/10 (20%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        2/30 (7%)        17/30 (57%)      19/29 (66%)      17/30 (57%)      16/30 (53%)      19/30 (63%)     | 
|FIRST INCIDENCE    |        186 (I)          366 (T)          366 (T)          366 (T)          366 (T)          366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.063          P<0.001 **       P<0.001 **       P<0.001 **       P=0.002 **       P<0.001 **      | 
|POLY 3             |        P=0.037 *        P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 1.5           |        P=0.044 *        P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 6             |        P=0.034 *        P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        P=0.062          P<0.001 **       P<0.001 **       P<0.001 **       P=0.002 **       P<0.001 **      | 
|COCH-ARM / FISHERS |        P=0.076          P<0.001 **       P<0.001 **       P<0.001 **       P=0.002 **       P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolus                                                                                                                   | 
|     Infiltration Cellular Histiocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        0/40 (0%)        1/40 (3%)        0/40 (0%)        0/40 (0%)        2/40 (5%)       | 
|POLY-3 RATE (b)    |        0/31.31          0/31.31          1/31.27          0/31.31          0/31.31          2/32.18         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             3.2%             0.0%             0.0%             6.2%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        1/10 (10%)       0/10 (0%)        0/10 (0%)        1/10 (10%)      | 
|TERMINAL (d)       |        0/30 (0%)        0/30 (0%)        0/29 (0%)        0/30 (0%)        0/30 (0%)        1/30 (3%)       | 
|FIRST INCIDENCE    |        ---              ---              186 (I)          ---              ---              186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.058          (e)              P=0.500          (e)              (e)              P=0.240         | 
|POLY 3             |        P=0.059          (e)              P=0.500          (e)              (e)              P=0.242         | 
|POLY 1.5           |        P=0.059          (e)              P=0.500          (e)              (e)              P=0.240         | 
|POLY 6             |        P=0.059          (e)              P=0.500          (e)              (e)              P=0.243         | 
|LOGISTIC REGRESSION|        P=0.055          (e)              P=0.536          (e)              (e)              P=0.236         | 
|COCH-ARM / FISHERS |        P=0.058          (e)              P=0.500          (e)              (e)              P=0.247         | 
|ORDER RESTRICTED   |        P=0.033 *        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 11      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Peribronchial                                                                                                              | 
|     Hyperplasia Focal Lymphoid                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        2/40 (5%)        3/40 (8%)        0/40 (0%)        0/40 (0%)        4/40 (10%)      | 
|POLY-3 RATE (b)    |        0/31.31          2/31.31          3/30.40          0/31.31          0/31.31          4/33.92         | 
|POLY-3 PERCENT (g) |        0.0%             6.4%             9.9%             0.0%             0.0%             11.8%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        3/10 (30%)      | 
|TERMINAL (d)       |        0/30 (0%)        2/30 (7%)        3/29 (10%)       0/30 (0%)        0/30 (0%)        1/30 (3%)       | 
|FIRST INCIDENCE    |        ---              366 (T)          366 (T)          ---              ---              186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.066          P=0.238          P=0.114          (e)              (e)              P=0.059         | 
|POLY 3             |        P=0.070          P=0.236          P=0.111          (e)              (e)              P=0.069         | 
|POLY 1.5           |        P=0.067          P=0.236          P=0.113          (e)              (e)              P=0.066         | 
|POLY 6             |        P=0.071          P=0.236          P=0.110          (e)              (e)              P=0.071         | 
|LOGISTIC REGRESSION|        P=0.064          P=0.238          P=0.114          (e)              (e)              P=0.055         | 
|COCH-ARM / FISHERS |        P=0.064          P=0.247          P=0.120          (e)              (e)              P=0.058         | 
|ORDER RESTRICTED   |        P=0.014 *        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Peribronchial                                                                                                              | 
|     Hyperplasia Lymphoid Focal                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/40 (13%)       8/40 (20%)       7/40 (18%)       7/40 (18%)       4/40 (10%)       1/40 (3%)       | 
|POLY-3 RATE (b)    |        5/35.66          8/31.31          7/30.40          7/31.31          4/31.31          1/31.31         | 
|POLY-3 PERCENT (g) |        14.0%            25.6%            23.0%            22.4%            12.8%            3.2%            | 
|INT SACRIFICE 1 (c)|        5/10 (50%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/30 (0%)        8/30 (27%)       7/29 (24%)       7/30 (23%)       4/30 (13%)       1/30 (3%)       | 
|FIRST INCIDENCE    |        186 (I)          366 (T)          366 (T)          366 (T)          366 (T)          366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.013N*        P=0.273          P=0.363          P=0.377          P=0.500N         P=0.089N        | 
|POLY 3             |        P=0.015N*        P=0.191          P=0.268          P=0.287          P=0.582N         P=0.132N        | 
|POLY 1.5           |        P=0.014N*        P=0.213          P=0.299          P=0.313          P=0.557N         P=0.121N        | 
|POLY 6             |        P=0.016N*        P=0.179          P=0.253          P=0.273          P=0.595N         P=0.138N        | 
|LOGISTIC REGRESSION|        P=0.012N*        P=0.270          P=0.392          P=0.376          P=0.500N         P=0.084N        | 
|COCH-ARM / FISHERS |        P=0.013N*        P=0.273          P=0.378          P=0.378          P=0.500N         P=0.100N        | 
|ORDER RESTRICTED   |        P=0.032N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 12      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Perivascular                                                                                                               | 
|     Hyperplasia Focal Lymphoid                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        1/40 (3%)        0/40 (0%)        2/40 (5%)        2/40 (5%)        2/40 (5%)       | 
|POLY-3 RATE (b)    |        1/32.18          1/32.18          0/30.40          2/31.31          2/31.31          2/32.18         | 
|POLY-3 PERCENT (g) |        3.1%             3.1%             0.0%             6.4%             6.4%             6.2%            | 
|INT SACRIFICE 1 (c)|        1/10 (10%)       1/10 (10%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)      | 
|TERMINAL (d)       |        0/30 (0%)        0/30 (0%)        0/29 (0%)        2/30 (7%)        2/30 (7%)        1/30 (3%)       | 
|FIRST INCIDENCE    |        186 (I)          186 (I)          ---              366 (T)          366 (T)          186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.290          P=0.766          P=0.500N         P=0.500          P=0.500          P=0.500         | 
|POLY 3             |        P=0.298          P=0.761          P=0.511N         P=0.490          P=0.490          P=0.500         | 
|POLY 1.5           |        P=0.295          P=0.761          P=0.508N         P=0.493          P=0.493          P=0.500         | 
|POLY 6             |        P=0.300          P=0.761          P=0.513N         P=0.489          P=0.489          P=0.500         | 
|LOGISTIC REGRESSION|        P=0.285          (e)              P=0.464N         P=0.500          P=0.500          P=0.500         | 
|COCH-ARM / FISHERS |        P=0.287          P=0.753N         P=0.500N         P=0.500          P=0.500          P=0.500         | 
|ORDER RESTRICTED   |        P=0.361          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Perivascular                                                                                                               | 
|     Hyperplasia Lymphoid Focal                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        15/40 (38%)      23/40 (57%)      25/40 (63%)      20/40 (50%)      17/40 (43%)      23/40 (57%)     | 
|POLY-3 RATE (b)    |        15/35.66         23/32.18         25/32.14         20/32.18         17/33.92         23/31.31        | 
|POLY-3 PERCENT (g) |        42.1%            71.5%            77.8%            62.2%            50.1%            73.5%           | 
|INT SACRIFICE 1 (c)|        5/10 (50%)       1/10 (10%)       2/10 (20%)       1/10 (10%)       3/10 (30%)       0/10 (0%)       | 
|TERMINAL (d)       |        10/30 (33%)      22/30 (73%)      23/29 (79%)      19/30 (63%)      14/30 (47%)      23/30 (77%)     | 
|FIRST INCIDENCE    |        186 (I)          186 (I)          186 (I)          186 (I)          186 (I)          366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.342          P=0.057          P=0.015 *        P=0.183          P=0.411          P=0.054         | 
|POLY 3             |        P=0.176          P=0.011 *        P=0.002 **       P=0.076          P=0.333          P=0.007 **      | 
|POLY 1.5           |        P=0.220          P=0.019 *        P=0.004 **       P=0.101          P=0.355          P=0.014 *       | 
|POLY 6             |        P=0.156          P=0.009 **       P<0.001 **       P=0.066          P=0.322          P=0.005 **      | 
|LOGISTIC REGRESSION|        P=0.337          P=0.055          P=0.017 *        P=0.181          P=0.410          P=0.052         | 
|COCH-ARM / FISHERS |        P=0.335          P=0.058          P=0.022 *        P=0.184          P=0.410          P=0.058         | 
|ORDER RESTRICTED   |        P=0.004 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 13      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Bronchial                                                                                                            | 
|     Congestion                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        17/32 (53%)      0/10 (0%)        0/11 (0%)        0/10 (0%)        0/11 (0%)        19/37 (51%)     | 
|POLY-3 RATE (b)    |        17/32.00         0/1.31           0/1.40           0/1.31           0/2.31           19/35.26        | 
|POLY-3 PERCENT (g) |        53.1%            0.0%             0.0%             0.0%             0.0%             53.9%           | 
|INT SACRIFICE 1 (c)|        9/9 (100%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        8/10 (80%)      | 
|TERMINAL (d)       |        8/23 (35%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/1 (0%)         11/27 (41%)     | 
|FIRST INCIDENCE    |        186 (I)          ---              ---              ---              ---              186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.022 *        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P=0.563N        | 
|POLY 3             |        P=0.488          P=0.450N         P=0.440N         P=0.450N         P=0.321N         P=0.572         | 
|POLY 1.5           |        P=0.307          P=0.171N         P=0.154N         P=0.171N         P=0.107N         P=0.594         | 
|POLY 6             |        P=0.513          P=0.615N         P=0.610N         P=0.615N         P=0.472N         P=0.561         | 
|LOGISTIC REGRESSION|        P=0.020 *        P<0.001N**       P<0.001N**       P<0.001N**       P<0.001N**       P=0.563N        | 
|COCH-ARM / FISHERS |        P=0.011 *        P=0.002N**       P<0.001N**       P=0.002N**       P<0.001N**       P=0.538N        | 
|ORDER RESTRICTED   |        P=0.157          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Bronchial                                                                                                            | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/32 (3%)        0/10 (0%)        0/11 (0%)        0/10 (0%)        1/11 (9%)        6/37 (16%)      | 
|POLY-3 RATE (b)    |        1/25.05          0/1.31           0/1.40           0/1.31           1/2.31           6/28.31         | 
|POLY-3 PERCENT (g) |        4.0%             0.0%             0.0%             0.0%             43.2%            21.2%           | 
|INT SACRIFICE 1 (c)|        1/9 (11.1%)      0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/23 (0%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         1/1 (100%)       6/27 (22%)      | 
|FIRST INCIDENCE    |        186 (I)          ---              ---              ---              366 (T)          366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.061          P=0.479N         P=0.479N         P=0.479N         P=0.550          P=0.084         | 
|POLY 3             |        P=0.025 *        P=0.832N         P=0.823N         P=0.832N         P=0.302          P=0.070         | 
|POLY 1.5           |        P=0.021 *        P=0.805N         P=0.793N         P=0.805N         P=0.369          P=0.073         | 
|POLY 6             |        P=0.025 *        P=0.845N         P=0.836N         P=0.845N         P=0.267          P=0.069         | 
|LOGISTIC REGRESSION|        P=0.059          (e)              P=0.450N         (e)              P=0.552          P=0.082         | 
|COCH-ARM / FISHERS |        P=0.008 **       P=0.762N         P=0.744N         P=0.762N         P=0.451          P=0.078         | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 14      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Congestion                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/35 (3%)        0/10 (0%)        0/12 (0%)        1/11 (9%)        0/10 (0%)        3/40 (8%)       | 
|POLY-3 RATE (b)    |        1/27.18          0/1.31           0/2.40           1/3.18           0/1.31           3/33.05         | 
|POLY-3 PERCENT (g) |        3.7%             0.0%             0.0%             31.4%            0.0%             9.1%            | 
|INT SACRIFICE 1 (c)|        0/9 (0%)         0/10 (0%)        0/10 (0%)        1/10 (10%)       0/10 (0%)        2/10 (20%)      | 
|TERMINAL (d)       |        1/26 (4%)        0/0 (0%)         0/1 (0%)         0/1 (0%)         0/0 (0%)         1/30 (3%)       | 
|FIRST INCIDENCE    |        366 (T)          ---              ---              186 (I)          ---              186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.145          P=1.000          P=0.993N         P=0.547          P=1.000          P=0.351         | 
|POLY 3             |        P=0.302          P=0.842N         P=0.813N         P=0.317          P=0.842N         P=0.377         | 
|POLY 1.5           |        P=0.287          P=0.816N         P=0.785N         P=0.372          P=0.816N         P=0.369         | 
|POLY 6             |        P=0.309          P=0.853N         P=0.826N         P=0.288          P=0.853N         P=0.381         | 
|LOGISTIC REGRESSION|        P=0.140          (e)              (e)              P=0.548          (e)              P=0.348         | 
|COCH-ARM / FISHERS |        P=0.192          P=0.778N         P=0.745N         P=0.425          P=0.778N         P=0.360         | 
|ORDER RESTRICTED   |        P=0.058          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        8/35 (23%)       0/10 (0%)        1/12 (8%)        0/11 (0%)        0/10 (0%)        5/40 (13%)      | 
|POLY-3 RATE (b)    |        8/28.05          0/1.31           1/2.40           0/2.31           0/1.31           5/31.31         | 
|POLY-3 PERCENT (g) |        28.5%            0.0%             41.7%            0.0%             0.0%             16.0%           | 
|INT SACRIFICE 1 (c)|        1/9 (11.1%)      0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        7/26 (27%)       0/0 (0%)         1/1 (100%)       0/1 (0%)         0/0 (0%)         5/30 (17%)      | 
|FIRST INCIDENCE    |        186 (I)          ---              366 (T)          ---              ---              366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.160N         P=0.479N         P=0.683          P=0.334N         P=0.479N         P=0.185N        | 
|POLY 3             |        P=0.121N         P=0.552N         P=0.570          P=0.461N         P=0.552N         P=0.196N        | 
|POLY 1.5           |        P=0.194N         P=0.365N         P=0.578N         P=0.298N         P=0.365N         P=0.194N        | 
|POLY 6             |        P=0.111N         P=0.654N         P=0.459          P=0.558N         P=0.654N         P=0.199N        | 
|LOGISTIC REGRESSION|        P=0.158N         P=0.478N         P=0.697          P=0.330N         P=0.478N         P=0.183N        | 
|COCH-ARM / FISHERS |        P=0.517N         P=0.109N         P=0.259N         P=0.090N         P=0.109N         P=0.190N        | 
|ORDER RESTRICTED   |        P=0.018N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 15      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mediastinal                                                                                                          | 
|     Congestion                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        20/35 (57%)      3/15 (20%)       1/12 (8%)        0/11 (0%)        1/10 (10%)       17/30 (57%)     | 
|POLY-3 RATE (b)    |        20/35.00         3/7.18           1/3.27           0/2.31           1/2.18           17/30.00        | 
|POLY-3 PERCENT (g) |        57.1%            41.8%            30.6%            0.0%             45.9%            56.7%           | 
|INT SACRIFICE 1 (c)|        8/8 (100%)       1/10 (10%)       1/10 (10%)       0/10 (0%)        1/10 (10%)       6/6 (100%)      | 
|TERMINAL (d)       |        12/27 (44%)      2/5 (40%)        0/1 (0%)         0/1 (0%)         0/0 (0%)         11/24 (46%)     | 
|FIRST INCIDENCE    |        186 (I)          186 (I)          186 (I)          ---              186 (I)          186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.062          P=0.007N**       P<0.001N**       P<0.001N**       P<0.001N**       P=0.572         | 
|POLY 3             |        P=0.492          P=0.394N         P=0.419N         P=0.298N         P=0.578N         P=0.583N        | 
|POLY 1.5           |        P=0.303          P=0.194N         P=0.162N         P=0.085N         P=0.278N         P=0.583N        | 
|POLY 6             |        P=0.556          P=0.515N         P=0.575N         P=0.459N         P=0.549          P=0.583N        | 
|LOGISTIC REGRESSION|        P=0.058          P=0.006N**       P<0.001N**       P<0.001N**       P<0.001N**       (e)             | 
|COCH-ARM / FISHERS |        P=0.030 *        P=0.016N*        P=0.003N**       P<0.001N**       P=0.009N**       P=0.584N        | 
|ORDER RESTRICTED   |        P=0.262N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mediastinal                                                                                                          | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/35 (14%)       4/15 (27%)       1/12 (8%)        1/11 (9%)        0/10 (0%)        8/30 (27%)      | 
|POLY-3 RATE (b)    |        5/31.53          4/6.31           1/2.40           1/2.31           0/1.31           8/24.79         | 
|POLY-3 PERCENT (g) |        15.9%            63.4%            41.7%            43.2%            0.0%             32.3%           | 
|INT SACRIFICE 1 (c)|        4/8 (50%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/6 (0%)        | 
|TERMINAL (d)       |        1/27 (4%)        4/5 (80%)        1/1 (100%)       1/1 (100%)       0/0 (0%)         8/24 (33%)      | 
|FIRST INCIDENCE    |        186 (I)          366 (T)          366 (T)          366 (T)          ---              366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.325          P=0.337          P=0.199N         P=0.199N         P=0.028N*        P=0.170         | 
|POLY 3             |        P=0.154          P=0.049 *        P=0.472          P=0.465          P=0.624N         P=0.129         | 
|POLY 1.5           |        P=0.168          P=0.092          P=0.611          P=0.598          P=0.499N         P=0.141         | 
|POLY 6             |        P=0.133          P=0.034 *        P=0.399          P=0.395          P=0.685N         P=0.123         | 
|LOGISTIC REGRESSION|        P=0.322          P=0.333          P=0.165N         P=0.192N         P=0.025N*        P=0.166         | 
|COCH-ARM / FISHERS |        P=0.120          P=0.254          P=0.514N         P=0.555N         P=0.266N         P=0.175         | 
|ORDER RESTRICTED   |        P=0.003 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 16      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mediastinal                                                                                                          | 
|     Pigmentation Hemosiderin                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        6/35 (17%)       0/15 (0%)        0/12 (0%)        0/11 (0%)        0/10 (0%)        2/30 (7%)       | 
|POLY-3 RATE (b)    |        6/29.79          0/6.31           0/2.40           0/2.31           0/1.31           2/24.79         | 
|POLY-3 PERCENT (g) |        20.1%            0.0%             0.0%             0.0%             0.0%             8.1%            | 
|INT SACRIFICE 1 (c)|        2/8 (25%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/6 (0%)        | 
|TERMINAL (d)       |        4/27 (15%)       0/5 (0%)         0/1 (0%)         0/1 (0%)         0/0 (0%)         2/24 (8%)       | 
|FIRST INCIDENCE    |        186 (I)          ---              ---              ---              ---              366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.327N         P=0.101N         P=0.163N         P=0.163N         P=0.185N         P=0.189N        | 
|POLY 3             |        P=0.147N         P=0.303N         P=0.520N         P=0.526N         P=0.596N         P=0.192N        | 
|POLY 1.5           |        P=0.220N         P=0.222N         P=0.377N         P=0.391N         P=0.449N         P=0.189N        | 
|POLY 6             |        P=0.123N         P=0.354N         P=0.597N         P=0.600N         P=0.672N         P=0.194N        | 
|LOGISTIC REGRESSION|        P=0.326N         P=0.096N         P=0.142N         P=0.156N         P=0.178N         P=0.185N        | 
|COCH-ARM / FISHERS |        P=0.459N         P=0.102N         P=0.151N         P=0.173N         P=0.199N         P=0.185N        | 
|ORDER RESTRICTED   |        P=0.006N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/3 (33%)        0/10 (0%)        0/10 (0%)        0/11 (0%)        0/10 (0%)        2/3 (67%)       | 
|POLY-3 RATE (b)    |        1/3.00           0/1.31           0/1.31           0/2.31           0/1.31           2/2.13          | 
|POLY-3 PERCENT (g) |        33.3%            0.0%             0.0%             0.0%             0.0%             93.8%           | 
|INT SACRIFICE 1 (c)|        1/1 (100%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        1/2 (50%)       | 
|TERMINAL (d)       |        0/2 (0%)         0/0 (0%)         0/0 (0%)         0/1 (0%)         0/0 (0%)         1/1 (100%)      | 
|FIRST INCIDENCE    |        186 (I)          ---              ---              ---              ---              186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.019 *        P=0.077N         P=0.077N         P=0.077N         P=0.077N         P=0.599         | 
|POLY 3             |        P=0.003 **       P=0.637N         P=0.637N         P=0.553N         P=0.637N         P=0.327         | 
|POLY 1.5           |        P<0.001 **       P=0.456N         P=0.456N         P=0.394N         P=0.456N         P=0.383         | 
|POLY 6             |        P=0.005 **       P=0.727N         P=0.727N         P=0.644N         P=0.727N         P=0.297         | 
|LOGISTIC REGRESSION|        P=0.012 *        (e)              (e)              (e)              (e)              P=0.620         | 
|COCH-ARM / FISHERS |        P=0.002 **       P=0.231N         P=0.231N         P=0.214N         P=0.231N         P=0.500         | 
|ORDER RESTRICTED   |        P=0.006 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 17      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mesentery                                                                                                                        | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/1 (100%)       2/2 (100%)       0/2 (0%)         2/2 (100%)       2/2 (100%)       0/1 (0%)        | 
|POLY-3 RATE (b)    |        1/1.00           2/2.00           0/0.22           2/2.00           2/2.00           0/0.13          | 
|POLY-3 PERCENT (g) |        100.0%           100.0%           0.0%             100.0%           100.0%           0.0%            | 
|INT SACRIFICE 1 (c)|        0/0 (0%)         0/0 (0%)         0/1 (0%)         1/1 (100%)       0/0 (0%)         0/1 (0%)        | 
|TERMINAL (d)       |        1/1 (100%)       2/2 (100%)       0/0 (0%)         1/1 (100%)       2/2 (100%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        366 (T)          366 (T)          ---              186 (I)          366 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.559N         (e)              P=1.000          (e)              (e)              P=1.000         | 
|POLY 3             |        P=1.000N         (e)              P=1.000N         (e)              (e)              P=1.000         | 
|POLY 1.5           |        P=0.955N         (e)              P=1.000N         (e)              (e)              P=1.000         | 
|POLY 6             |        P=1.000N         (e)              P=1.000N         (e)              (e)              P=1.000         | 
|LOGISTIC REGRESSION|        P=0.559N         (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.365N         (e)              P=0.333N         (e)              (e)              P=0.500N        | 
|ORDER RESTRICTED   |        P=0.014N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas                                                                                                                         | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        8/40 (20%)       0/10 (0%)        0/11 (0%)        0/10 (0%)        0/10 (0%)        9/40 (23%)      | 
|POLY-3 RATE (b)    |        8/31.31          0/1.31           0/1.40           0/1.31           0/1.31           9/32.18         | 
|POLY-3 PERCENT (g) |        25.6%            0.0%             0.0%             0.0%             0.0%             28.0%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)      | 
|TERMINAL (d)       |        8/30 (27%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         8/30 (27%)      | 
|FIRST INCIDENCE    |        366 (T)          ---              ---              ---              ---              186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.407          P=1.000          P=1.000          P=1.000          P=1.000          P=0.500         | 
|POLY 3             |        P=0.443          P=0.566N         P=0.557N         P=0.566N         P=0.566N         P=0.526         | 
|POLY 1.5           |        P=0.324          P=0.394N         P=0.376N         P=0.394N         P=0.394N         P=0.518         | 
|POLY 6             |        P=0.468          P=0.660N         P=0.654N         P=0.660N         P=0.660N         P=0.531         | 
|LOGISTIC REGRESSION|        P=0.406          (e)              (e)              (e)              (e)              P=0.500         | 
|COCH-ARM / FISHERS |        P=0.083          P=0.143N         P=0.121N         P=0.143N         P=0.143N         P=0.500         | 
|ORDER RESTRICTED   |        P=0.307          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 18      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas                                                                                                                         | 
|     Atrophy Focal                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/40 (5%)        0/10 (0%)        0/11 (0%)        0/10 (0%)        0/10 (0%)        1/40 (3%)       | 
|POLY-3 RATE (b)    |        2/32.18          0/1.31           0/1.40           0/1.31           0/1.31           1/31.31         | 
|POLY-3 PERCENT (g) |        6.2%             0.0%             0.0%             0.0%             0.0%             3.2%            | 
|INT SACRIFICE 1 (c)|        1/10 (10%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        1/30 (3%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         1/30 (3%)       | 
|FIRST INCIDENCE    |        186 (I)          ---              ---              ---              ---              366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.551N         P=0.500N         P=0.500N         P=0.500N         P=0.500N         P=0.500N        | 
|POLY 3             |        P=0.392N         P=0.758N         P=0.748N         P=0.758N         P=0.758N         P=0.510N        | 
|POLY 1.5           |        P=0.450N         P=0.703N         P=0.689N         P=0.703N         P=0.703N         P=0.507N        | 
|POLY 6             |        P=0.377N         P=0.785N         P=0.776N         P=0.785N         P=0.785N         P=0.511N        | 
|LOGISTIC REGRESSION|        P=0.553N         P=0.500N         P=0.482N         P=0.500N         P=0.500N         P=0.500N        | 
|COCH-ARM / FISHERS |        P=0.621N         P=0.637N         P=0.612N         P=0.637N         P=0.637N         P=0.500N        | 
|ORDER RESTRICTED   |        P=0.229N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas                                                                                                                         | 
|     Infiltration Cellular Mixed Cell                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/40 (5%)        0/10 (0%)        0/11 (0%)        0/10 (0%)        0/10 (0%)        2/40 (5%)       | 
|POLY-3 RATE (b)    |        2/31.31          0/1.31           0/1.40           0/1.31           0/1.31           2/33.05         | 
|POLY-3 PERCENT (g) |        6.4%             0.0%             0.0%             0.0%             0.0%             6.1%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        2/10 (20%)      | 
|TERMINAL (d)       |        2/30 (7%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/30 (0%)       | 
|FIRST INCIDENCE    |        366 (T)          ---              ---              ---              ---              186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.421          P=1.000          P=1.000          P=1.000          P=1.000          P=0.695         | 
|POLY 3             |        P=0.612N         P=0.757N         P=0.747N         P=0.757N         P=0.757N         P=0.675N        | 
|POLY 1.5           |        P=0.595          P=0.702N         P=0.688N         P=0.702N         P=0.702N         P=0.681N        | 
|POLY 6             |        P=0.593N         P=0.785N         P=0.776N         P=0.785N         P=0.785N         P=0.672N        | 
|LOGISTIC REGRESSION|        P=0.417          (e)              (e)              (e)              (e)              P=0.698N        | 
|COCH-ARM / FISHERS |        P=0.418          P=0.637N         P=0.612N         P=0.637N         P=0.637N         P=0.692N        | 
|ORDER RESTRICTED   |        P=0.659N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 19      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland                                                                                                                  | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        11/40 (28%)      1/18 (6%)        0/14 (0%)        0/14 (0%)        1/14 (7%)        11/40 (28%)     | 
|POLY-3 RATE (b)    |        11/32.18         1/9.31           0/4.40           0/5.31           1/5.31           11/31.31        | 
|POLY-3 PERCENT (g) |        34.2%            10.7%            0.0%             0.0%             18.8%            35.1%           | 
|INT SACRIFICE 1 (c)|        1/10 (10%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        10/30 (33%)      1/8 (13%)        0/3 (0%)         0/4 (0%)         1/4 (25%)        11/30 (37%)     | 
|FIRST INCIDENCE    |        186 (I)          366 (T)          ---              ---              366 (T)          366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.225          P=0.148N         P=0.161N         P=0.120N         P=0.387N         P=0.602         | 
|POLY 3             |        P=0.274          P=0.191N         P=0.258N         P=0.199N         P=0.439N         P=0.573         | 
|POLY 1.5           |        P=0.174          P=0.129N         P=0.139N         P=0.112N         P=0.298N         P=0.582         | 
|POLY 6             |        P=0.332          P=0.235N         P=0.344N         P=0.265N         P=0.525N         P=0.568         | 
|LOGISTIC REGRESSION|        P=0.224          P=0.144N         P=0.152N         P=0.116N         P=0.385N         P=0.603N        | 
|COCH-ARM / FISHERS |        P=0.058          P=0.053N         P=0.024N*        P=0.024N*        P=0.111N         P=0.599N        | 
|ORDER RESTRICTED   |        P=0.082          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        0/18 (0%)        1/14 (7%)        0/14 (0%)        0/14 (0%)        2/40 (5%)       | 
|POLY-3 RATE (b)    |        1/32.18          0/9.31           1/4.40           0/5.31           0/5.31           2/32.18         | 
|POLY-3 PERCENT (g) |        3.1%             0.0%             22.7%            0.0%             0.0%             6.2%            | 
|INT SACRIFICE 1 (c)|        1/10 (10%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)      | 
|TERMINAL (d)       |        0/30 (0%)        0/8 (0%)         1/3 (33%)        0/4 (0%)         0/4 (0%)         1/30 (3%)       | 
|FIRST INCIDENCE    |        186 (I)          ---              366 (T)          ---              ---              186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.316          P=0.500N         P=0.563          P=0.500N         P=0.500N         P=0.500         | 
|POLY 3             |        P=0.383          P=0.720N         P=0.341          P=0.784N         P=0.784N         P=0.500         | 
|POLY 1.5           |        P=0.376          P=0.701N         P=0.396          P=0.762N         P=0.762N         P=0.500         | 
|POLY 6             |        P=0.383          P=0.731N         P=0.313          P=0.796N         P=0.796N         P=0.500         | 
|LOGISTIC REGRESSION|        P=0.312          (e)              P=0.580          (e)              (e)              P=0.500         | 
|COCH-ARM / FISHERS |        P=0.335          P=0.690N         P=0.455          P=0.741N         P=0.741N         P=0.500         | 
|ORDER RESTRICTED   |        P=0.231          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 20      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Preputial Gland                                                                                                                  | 
|     Infiltration Cellular Mixed Cell                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/39 (5%)        0/10 (0%)        0/10 (0%)        2/12 (17%)       0/10 (0%)        1/40 (3%)       | 
|POLY-3 RATE (b)    |        2/30.31          0/1.31           0/1.31           2/3.31           0/1.31           1/31.31         | 
|POLY-3 PERCENT (g) |        6.6%             0.0%             0.0%             60.4%            0.0%             3.2%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        2/29 (7%)        0/0 (0%)         0/0 (0%)         2/2 (100%)       0/0 (0%)         1/30 (3%)       | 
|FIRST INCIDENCE    |        366 (T)          ---              ---              366 (T)          ---              366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.193N         P=1.000          P=1.000N         P=0.004 **       P=1.000          P=0.488N        | 
|POLY 3             |        P=0.281N         P=0.754N         P=0.754N         P=0.087          P=0.754N         P=0.489N        | 
|POLY 1.5           |        P=0.286N         P=0.697N         P=0.697N         P=0.129          P=0.697N         P=0.489N        | 
|POLY 6             |        P=0.296N         P=0.782N         P=0.782N         P=0.069          P=0.782N         P=0.488N        | 
|LOGISTIC REGRESSION|        P=0.193N         (e)              (e)              P=0.004 **       (e)              P=0.488N        | 
|COCH-ARM / FISHERS |        P=0.378N         P=0.630N         P=0.630N         P=0.232          P=0.630N         P=0.490N        | 
|ORDER RESTRICTED   |        P=0.034N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Preputial Gland                                                                                                                  | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        3/39 (8%)        0/10 (0%)        0/10 (0%)        2/12 (17%)       0/10 (0%)        0/40 (0%)       | 
|POLY-3 RATE (b)    |        3/31.18          0/1.31           0/1.31           2/3.31           0/1.31           0/31.31         | 
|POLY-3 PERCENT (g) |        9.6%             0.0%             0.0%             60.4%            0.0%             0.0%            | 
|INT SACRIFICE 1 (c)|        1/10 (10%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        2/29 (7%)        0/0 (0%)         0/0 (0%)         2/2 (100%)       0/0 (0%)         0/30 (0%)       | 
|FIRST INCIDENCE    |        186 (I)          ---              ---              366 (T)          ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.052N         P=0.500N         P=0.500N         P=0.139          P=0.500N         P=0.119N        | 
|POLY 3             |        P=0.043N*        P=0.698N         P=0.698N         P=0.131          P=0.698N         P=0.116N        | 
|POLY 1.5           |        P=0.047N*        P=0.615N         P=0.615N         P=0.193          P=0.615N         P=0.115N        | 
|POLY 6             |        P=0.047N*        P=0.739N         P=0.739N         P=0.103          P=0.739N         P=0.116N        | 
|LOGISTIC REGRESSION|        P=0.050N         P=0.500N         P=0.500N         P=0.134          P=0.500N         P=0.115N        | 
|COCH-ARM / FISHERS |        P=0.093N         P=0.496N         P=0.496N         P=0.335          P=0.496N         P=0.116N        | 
|ORDER RESTRICTED   |        P<0.001N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 21      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Prostate                                                                                                                         | 
|     Corpora Amylacea                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/40 (3%)        0/10 (0%)        0/11 (0%)        0/10 (0%)        0/10 (0%)        2/40 (5%)       | 
|POLY-3 RATE (b)    |        1/32.18          0/1.31           0/1.40           0/1.31           0/1.31           2/33.05         | 
|POLY-3 PERCENT (g) |        3.1%             0.0%             0.0%             0.0%             0.0%             6.1%            | 
|INT SACRIFICE 1 (c)|        1/10 (10%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        2/10 (20%)      | 
|TERMINAL (d)       |        0/30 (0%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/30 (0%)       | 
|FIRST INCIDENCE    |        186 (I)          ---              ---              ---              ---              186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.062          P=0.500N         P=0.500N         P=0.500N         P=0.500N         P=0.500         | 
|POLY 3             |        P=0.372          P=0.856N         P=0.847N         P=0.856N         P=0.856N         P=0.509         | 
|POLY 1.5           |        P=0.347          P=0.835N         P=0.823N         P=0.835N         P=0.835N         P=0.506         | 
|POLY 6             |        P=0.373          P=0.866N         P=0.857N         P=0.866N         P=0.866N         P=0.511         | 
|LOGISTIC REGRESSION|        P=0.056          (e)              P=0.470N         (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.238          P=0.800N         P=0.784N         P=0.800N         P=0.800N         P=0.500         | 
|ORDER RESTRICTED   |        P=0.230          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Prostate                                                                                                                         | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/40 (0%)        0/10 (0%)        0/11 (0%)        0/10 (0%)        0/10 (0%)        2/40 (5%)       | 
|POLY-3 RATE (b)    |        0/31.31          0/1.31           0/1.40           0/1.31           0/1.31           2/31.31         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             6.4%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/30 (0%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         2/30 (7%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.174          (e)              (e)              (e)              (e)              P=0.238         | 
|POLY 3             |        P=0.098          (e)              (e)              (e)              (e)              P=0.236         | 
|POLY 1.5           |        P=0.096          (e)              (e)              (e)              (e)              P=0.236         | 
|POLY 6             |        P=0.096          (e)              (e)              (e)              (e)              P=0.236         | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              P=0.238         | 
|COCH-ARM / FISHERS |        P=0.073          (e)              (e)              (e)              (e)              P=0.247         | 
|ORDER RESTRICTED   |        P=0.009 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 22      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Accessory Spleen                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/40 (5%)        1/13 (8%)        1/12 (8%)        2/13 (15%)       3/13 (23%)       2/40 (5%)       | 
|POLY-3 RATE (b)    |        2/31.31          1/4.31           1/2.40           2/4.31           3/4.31           2/31.31         | 
|POLY-3 PERCENT (g) |        6.4%             23.2%            41.7%            46.4%            69.6%            6.4%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        2/30 (7%)        1/3 (33%)        1/1 (100%)       2/3 (67%)        3/3 (100%)       2/30 (7%)       | 
|FIRST INCIDENCE    |        366 (T)          366 (T)          366 (T)          366 (T)          366 (T)          366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.174N         P=0.319          P=0.086          P=0.019 *        P<0.001 **       P=0.696         | 
|POLY 3             |        P=0.374N         P=0.427          P=0.351          P=0.110          P=0.015 *        P=0.695         | 
|POLY 1.5           |        P=0.348N         P=0.497          P=0.436          P=0.152          P=0.027 *        P=0.695         | 
|POLY 6             |        P=0.411N         P=0.389          P=0.307          P=0.091          P=0.011 *        P=0.695         | 
|LOGISTIC REGRESSION|        P=0.174N         P=0.319          P=0.086          P=0.019 *        P<0.001 **       P=0.696         | 
|COCH-ARM / FISHERS |        P=0.408N         P=0.578          P=0.553          P=0.249          P=0.088          P=0.692N        | 
|ORDER RESTRICTED   |        P=0.013 *        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Interstitial Cell                                                                                                        | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        26/40 (65%)      31/40 (78%)      31/40 (78%)      31/40 (78%)      32/39 (82%)      40/40 (100%)    | 
|POLY-3 RATE (b)    |        26/32.18         31/32.18         31/33.01         31/32.18         32/32.92         40/40.00        | 
|POLY-3 PERCENT (g) |        80.8%            96.3%            93.9%            96.3%            97.2%            100.0%          | 
|INT SACRIFICE 1 (c)|        1/10 (10%)       1/10 (10%)       3/10 (30%)       1/10 (10%)       3/10 (30%)       10/10 (100%)    | 
|TERMINAL (d)       |        25/30 (83%)      30/30 (100%)     28/29 (97%)      30/30 (100%)     29/29 (100%)     30/30 (100%)    | 
|FIRST INCIDENCE    |        186 (I)          186 (I)          186 (I)          186 (I)          186 (I)          186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.059          P=0.050          P=0.059          P=0.018 *        P<0.001 **      | 
|POLY 3             |        P=0.006 **       P=0.033 *        P=0.083          P=0.033 *        P=0.022 *        P=0.003 **      | 
|POLY 1.5           |        P<0.001 **       P=0.059          P=0.095          P=0.059          P=0.028 *        P<0.001 **      | 
|POLY 6             |        P=0.056          P=0.028 *        P=0.089          P=0.028 *        P=0.025 *        P=0.011 *       | 
|LOGISTIC REGRESSION|        P<0.001 **       P=0.057          P=0.052          P=0.057          P=0.017 *        P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.162          P=0.162          P=0.162          P=0.072          P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/15/04                           EXPERIMENT: 05135 TEST: 05                                            Page 23      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                         ISOPRENE  
                                         Terminal Sacrifice at 53 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland                                                                                                                    | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/40 (5%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        3/40 (8%)       | 
|POLY-3 RATE (b)    |        2/33.05          0/1.31           0/1.31           0/1.31           0/1.31           3/32.18         | 
|POLY-3 PERCENT (g) |        6.1%             0.0%             0.0%             0.0%             0.0%             9.3%            | 
|INT SACRIFICE 1 (c)|        2/10 (20%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        1/10 (10%)      | 
|TERMINAL (d)       |        0/30 (0%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         2/30 (7%)       | 
|FIRST INCIDENCE    |        186 (I)          ---              ---              ---              ---              186 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.158          P=0.234N         P=0.234N         P=0.234N         P=0.234N         P=0.500         | 
|POLY 3             |        P=0.375          P=0.759N         P=0.759N         P=0.759N         P=0.759N         P=0.488         | 
|POLY 1.5           |        P=0.341          P=0.705N         P=0.705N         P=0.705N         P=0.705N         P=0.492         | 
|POLY 6             |        P=0.376          P=0.784N         P=0.784N         P=0.784N         P=0.784N         P=0.486         | 
|LOGISTIC REGRESSION|        P=0.156          (e)              (e)              (e)              (e)              P=0.500         | 
|COCH-ARM / FISHERS |        P=0.209          P=0.637N         P=0.637N         P=0.637N         P=0.637N         P=0.500         | 
|ORDER RESTRICTED   |        P=0.252          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          70 PPM           220 PPM          700 PPM          2200 PPM         7000 PPM        | 
|                   |                                                                                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Urinary Bladder                                                                                                                  | 
|     Calculus Micro Observation Only                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/40 (5%)        0/11 (0%)        3/13 (23%)       0/10 (0%)        5/17 (29%)       12/40 (30%)     | 
|POLY-3 RATE (b)    |        2/31.31          0/2.31           3/4.31           0/1.31           5/8.31           12/31.31        | 
|POLY-3 PERCENT (g) |        6.4%             0.0%             69.6%            0.0%             60.2%            38.3%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        2/30 (7%)        0/1 (0%)         3/3 (100%)       0/0 (0%)         5/7 (71%)        12/30 (40%)     | 
|FIRST INCIDENCE    |        366 (T)          ---              366 (T)          ---              366 (T)          366 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.038 *        P=0.962N         P<0.001 **       P=1.000N         P<0.001 **       P=0.003 **      | 
|POLY 3             |        P=0.003 **       P=0.724N         P=0.015 *        P=0.757N         P=0.002 **       P=0.002 **      | 
|POLY 1.5           |        P=0.003 **       P=0.669N         P=0.027 *        P=0.702N         P=0.003 **       P=0.002 **      | 
|POLY 6             |        P=0.003 **       P=0.752N         P=0.011 *        P=0.785N         P<0.001 **       P=0.002 **      | 
|LOGISTIC REGRESSION|        P=0.038 *        (e)              P<0.001 **       (e)              P<0.001 **       P=0.003 **      | 
|COCH-ARM / FISHERS |        P=0.002 **       P=0.612N         P=0.088          P=0.637N         P=0.020 *        P=0.003 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (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).