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TDMS Study 05161-05 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Southern Research Inst                                   RIDDELLIINE                                      DATE: 12/15/00       
EXPERIMENT: 05161 TEST: 05                                                                                     TIME: 12:16:38       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-55393                              ROUTE: GAVAGE                                                  NTP C#: 61358C       
PATHOLOGIST: HEATH, JAMES E.                                                                                   CAS: 23246-96-0      
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                        RATS/FINAL#1_FEMALES                                                        
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE 003    0       MG/KG/DY                                                              
                                       INCLUDE 004    0.01    MG/KG/DY                                                              
                                       INCLUDE 005    0.033   MG/KG/DY                                                              
                                       INCLUDE 006    0.1     MG/KG/DY                                                              
                                       INCLUDE 007    0.33    MG/KG/DY                                                              
                                       INCLUDE 008    1.0     MG/KG/DY                                                              
                                                                                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Southern Research Inst                                   RIDDELLIINE                                      DATE: 12/15/00       
EXPERIMENT: 05161 TEST: 05                                                                                     TIME: 12:16:38       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-55393                              ROUTE: GAVAGE                                                  NTP C#: 61358C       
PATHOLOGIST: HEATH, JAMES E.                                                                                   CAS: 23246-96-0      
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF                   RIDDELLIINE                                                                                    
===============================================================                                                                     
Female Rats                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Adrenal Cortex                         Accessory Adrenal Cortical Nodule                                                            
                                       Degeneration Fatty                                                                           
                                       Hyperplasia Focal                                                                            
                                       Hypertrophy Focal                                                                            
Bone Marrow                            Hyperplasia                                                                                  
Bone: Cranium                          Osteopetrosis                                                                                
Bone: Femur                            Osteopetrosis                                                                                
Brain                                  Compression                                                                                  
                                       Hydrocephalus                                                                                
Clitoral Gland                         Cyst                                                                                         
                                       Hyperplasia                                                                                  
                                       Inflammation Chronic                                                                         
Heart                                  Cardiomyopathy                                                                               
Kidney                                 Nephropathy                                                                                  
Kidney: Renal Tubule                   Hyaline Droplet                                                                              
                                       Necrosis                                                                                     
                                       Pigmentation                                                                                 
Kidney: Transitional Epithelium        Hyperplasia                                                                                  
Liver                                  Angiectasis                                                                                  
                                       Basophilic Focus                                                                             
                                       Clear Cell Focus                                                                             
                                       Eosinophilic Focus                                                                           
                                       Hematopoietic Cell Proliferation                                                             
                                       Hemorrhage                                                                                   
                                       Hepatodiaphragmatic Nodule                                                                   
                                       Infiltration Cellular Mixed Cell                                                             
                                       Mixed Cell Focus                                                                             
                                       Necrosis Focal                                                                               
Liver: Bile Duct                       Hyperplasia                                                                                  
Liver: Hepatocyte                      Cytomegaly                                                                                   
                                       Hyperplasia Regenerative                                                                     
                                       Vacuolization Cytoplasmic                                                                    
Liver: Kupffer Cell                    Pigmentation                                                                                 
Lung                                   Congestion                                                                                   
                                       Edema                                                                                        
                                       Hemorrhage                                                                                   
                                       Infiltration Cellular Histiocyte                                                             
Lung: Alveolar Epithelium              Hyperplasia                                                                                  
Lymph Node, Mandibular                 Pigmentation                                                                                 
Lymph Node, Mediastinal                Congestion                                                                                   
                                       Hemorrhage                                                                                   
                                       Pigmentation                                                                                 
Lymph Node, Mesenteric                 Hemorrhage                                                                                   
                                       Pigmentation                                                                                 
Lymph Node: Pancreatic                 Hemorrhage                                                                                   
                                       Pigmentation                                                                                 
Lymph Node: Renal                      Pigmentation                                                                                 
Mammary Gland                          Hyperplasia                                                                                  
                                                                                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Southern Research Inst                                   RIDDELLIINE                                      DATE: 12/15/00       
EXPERIMENT: 05161 TEST: 05                                                                                     TIME: 12:16:38       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-55393                              ROUTE: GAVAGE                                                  NTP C#: 61358C       
PATHOLOGIST: HEATH, JAMES E.                                                                                   CAS: 23246-96-0      
Mesentery: Fat                         Necrosis                                                                                     
Nose: Respiratory Epithelium           Hyperplasia                                                                                  
Ovary                                  Cyst                                                                                         
Pancreas                               Atrophy                                                                                      
Pituitary Gland: Pars Distalis         Angiectasis                                                                                  
                                       Cyst                                                                                         
                                       Hyperplasia Focal                                                                            
Salivary Glands                        Atrophy                                                                                      
Skeletal Muscle                        Hemorrhage                                                                                   
Spleen                                 Congestion                                                                                   
                                       Hematopoietic Cell Proliferation                                                             
                                       Pigmentation                                                                                 
Stomach, Forestomach: Epithelium       Hyperplasia                                                                                  
Stomach, Glandular                     Erosion                                                                                      
                                       Ulcer                                                                                        
Thymus                                 Hemorrhage                                                                                   
Thyroid Gland                          Ultimobranchial Cyst                                                                         
Thyroid Gland: C-Cell                  Hyperplasia                                                                                  
Uterus                                 Hydrometra                                                                                   
                                       Hyperplasia Cystic                                                                           
===============================================================                                                                     
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 1       
                     Statistical Analysis of Non-neoplastic Lesions in        Rats(FISCHER 344)  -                    RIDDELLIINE   
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Accessory Adrenal Cortical Nodule                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        6/50 (12%)       2/50 (4%)        6/50 (12%)       4/50 (8%)        2/50 (4%)        7/50 (14%)      | 
|POLY-3 RATE (b)    |        6/44.74          2/40.06          6/42.82          4/41.17          2/41.99          7/21.99         | 
|POLY-3 PERCENT (g) |        13.4%            5.0%             14.0%            9.7%             4.8%             31.8%           | 
|TERMINAL (d)       |        2/33 (6%)        1/22 (5%)        3/28 (11%)       2/22 (9%)        2/29 (7%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        437              698              571              646              729 (T)          426             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.229N         P=0.560          P=0.512N         P=0.169N         P=0.005 **      | 
|POLY 3             |        P=0.085          P=0.170N         P=0.590          P=0.422N         P=0.153N         P=0.092         | 
|POLY 1.5           |        P=0.117          P=0.153N         P=0.604          P=0.404N         P=0.143N         P=0.228         | 
|POLY 6             |        P=0.107          P=0.200N         P=0.568          P=0.452N         P=0.172N         P=0.023 *       | 
|LOGISTIC REGRESSION|        P=0.338          P=0.117N         P=0.616N         P=0.348N         P=0.137N         P=0.470N        | 
|COCH-ARM / FISHERS |        P=0.228          P=0.134N         P=0.620N         P=0.370N         P=0.134N         P=0.500         | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Degeneration Fatty                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        9/50 (18%)       9/50 (18%)       12/50 (24%)      8/50 (16%)       13/50 (26%)      3/50 (6%)       | 
|POLY-3 RATE (b)    |        9/43.20          9/40.47          12/43.77         8/41.95          13/44.52         3/18.97         | 
|POLY-3 PERCENT (g) |        20.8%            22.2%            27.4%            19.1%            29.2%            15.8%           | 
|TERMINAL (d)       |        8/33 (24%)       7/22 (32%)       7/28 (25%)       4/22 (18%)       7/29 (24%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        640              573              437              451              451              527             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.025 *        P=0.272          P=0.214          P=0.426          P=0.172          P=0.002 **      | 
|POLY 3             |        P=0.519          P=0.544          P=0.320          P=0.527N         P=0.254          P=0.461N        | 
|POLY 1.5           |        P=0.249N         P=0.573          P=0.321          P=0.518N         P=0.251          P=0.220N        | 
|POLY 6             |        P=0.246          P=0.491          P=0.309          P=0.550N         P=0.247          P=0.443         | 
|LOGISTIC REGRESSION|        P=0.347N         P=0.453          P=0.300          P=0.543N         P=0.232          P=0.304         | 
|COCH-ARM / FISHERS |        P=0.033N*        P=0.602N         P=0.312          P=0.500N         P=0.235          P=0.061N        | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 2       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hyperplasia Diffuse                                                                                                         | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/50 (0%)        0/50 (0%)        3/50 (6%)        1/50 (2%)        0/50 (0%)        0/50 (0%)       | 
|POLY-3 RATE (b)    |        0/42.87          0/39.94          3/43.16          1/40.87          0/41.99          0/17.60         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             7.0%             2.5%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        0/28 (0%)        0/22 (0%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              437              707              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.496N         (e)              P=0.124          P=0.455          (e)              (e)             | 
|POLY 3             |        P=0.299N         (e)              P=0.119          P=0.490          (e)              (e)             | 
|POLY 1.5           |        P=0.288N         (e)              P=0.120          P=0.494          (e)              (e)             | 
|POLY 6             |        P=0.355N         (e)              P=0.117          P=0.484          (e)              (e)             | 
|LOGISTIC REGRESSION|        P=0.135N         (e)              P=0.090          P=0.487          (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.263N         (e)              P=0.121          P=0.500          (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/50 (8%)        5/50 (10%)       6/50 (12%)       4/50 (8%)        9/50 (18%)       3/50 (6%)       | 
|POLY-3 RATE (b)    |        4/43.99          5/40.06          6/42.38          4/41.21          9/42.53          3/19.64         | 
|POLY-3 PERCENT (g) |        9.1%             12.5%            14.2%            9.7%             21.2%            15.3%           | 
|TERMINAL (d)       |        2/33 (6%)        4/22 (18%)       5/28 (18%)       2/22 (9%)        7/29 (24%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        437              698              444              668              630              407             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.002 **       P=0.315          P=0.302          P=0.513          P=0.088          P=0.148         | 
|POLY 3             |        P=0.166          P=0.441          P=0.345          P=0.607          P=0.100          P=0.399         | 
|POLY 1.5           |        P=0.401          P=0.468          P=0.359          P=0.619          P=0.108          P=0.584         | 
|POLY 6             |        P=0.051          P=0.400          P=0.321          P=0.588          P=0.087          P=0.210         | 
|LOGISTIC REGRESSION|        P=0.388          P=0.487          P=0.374          P=0.638N         P=0.116          P=0.285N        | 
|COCH-ARM / FISHERS |        P=0.363N         P=0.500          P=0.370          P=0.643N         P=0.117          P=0.500N        | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 3       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        9/50 (18%)       5/50 (10%)       7/50 (14%)       2/50 (4%)        4/50 (8%)        2/50 (4%)       | 
|POLY-3 RATE (b)    |        9/43.90          5/40.30          7/42.69          2/41.55          4/42.52          2/18.45         | 
|POLY-3 PERCENT (g) |        20.5%            12.4%            16.4%            4.8%             9.4%             10.8%           | 
|TERMINAL (d)       |        7/33 (21%)       3/22 (14%)       4/28 (14%)       1/22 (5%)        1/29 (3%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        483              643              532              451              671              528             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.369          P=0.416N         P=0.498N         P=0.079N         P=0.170N         P=0.157         | 
|POLY 3             |        P=0.203N         P=0.240N         P=0.415N         P=0.030N*        P=0.125N         P=0.319N        | 
|POLY 1.5           |        P=0.136N         P=0.218N         P=0.403N         P=0.029N*        P=0.120N         P=0.123N        | 
|POLY 6             |        P=0.231N         P=0.281N         P=0.438N         P=0.035N*        P=0.137N         P=0.588         | 
|LOGISTIC REGRESSION|        P=0.188N         P=0.230N         P=0.399N         P=0.027N*        P=0.119N         P=0.528N        | 
|COCH-ARM / FISHERS |        P=0.051N         P=0.194N         P=0.393N         P=0.026N*        P=0.117N         P=0.026N*       | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Medulla                                                                                                                  | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/50 (2%)        3/49 (6%)        0/50 (0%)        3/50 (6%)        3/50 (6%)        0/50 (0%)       | 
|POLY-3 RATE (b)    |        1/42.87          3/40.69          0/41.60          3/41.16          3/42.15          0/17.60         | 
|POLY-3 PERCENT (g) |        2.3%             7.4%             0.0%             7.3%             7.1%             0.0%            | 
|TERMINAL (d)       |        1/33 (3%)        1/22 (5%)        0/28 (0%)        1/22 (5%)        2/29 (7%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        729 (T)          407              ---              651              686              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.615          P=0.239          P=0.533N         P=0.219          P=0.263          P=1.000N        | 
|POLY 3             |        P=0.535          P=0.286          P=0.506N         P=0.290          P=0.299          P=0.650N        | 
|POLY 1.5           |        P=0.431N         P=0.293          P=0.503N         P=0.295          P=0.304          P=0.586N        | 
|POLY 6             |        P=0.314          P=0.272          P=0.513N         P=0.281          P=0.288          P=0.716N        | 
|LOGISTIC REGRESSION|        P=0.307N         P=0.329          (e)              P=0.284          P=0.275          (e)             | 
|COCH-ARM / FISHERS |        P=0.233N         P=0.301          P=0.500N         P=0.309          P=0.309          P=0.500N        | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 4       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone Marrow                                                                                                                      | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        6/50 (12%)       3/50 (6%)        8/50 (16%)       7/50 (14%)       10/50 (20%)      32/50 (64%)     | 
|POLY-3 RATE (b)    |        6/45.97          3/41.67          8/43.74          7/42.19          10/44.09         32/38.51        | 
|POLY-3 PERCENT (g) |        13.1%            7.2%             18.3%            16.6%            22.7%            83.1%           | 
|TERMINAL (d)       |        1/33 (3%)        0/22 (0%)        3/28 (11%)       3/22 (14%)       4/29 (14%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        393              407              437              307              524              350             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.297N         P=0.352          P=0.361          P=0.191          P<0.001 **      | 
|POLY 3             |        P<0.001 **       P=0.292N         P=0.348          P=0.434          P=0.178          P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       P=0.271N         P=0.364          P=0.457          P=0.190          P<0.001 **      | 
|POLY 6             |        P<0.001 **       P=0.325N         P=0.328          P=0.401          P=0.165          P<0.001 **      | 
|LOGISTIC REGRESSION|        P<0.001 **       P=0.152N         P=0.376          P=0.603          P=0.175          P=0.046 *       | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.243N         P=0.387          P=0.500          P=0.207          P<0.001 **      | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone: Cranium                                                                                                                    | 
|     Osteopetrosis                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        10/50 (20%)      10/50 (20%)      12/50 (24%)      6/50 (12%)       7/50 (14%)       0/50 (0%)       | 
|POLY-3 RATE (b)    |        10/43.13         10/41.68         12/42.66         6/40.84          7/42.15          0/17.60         | 
|POLY-3 PERCENT (g) |        23.2%            24.0%            28.1%            14.7%            16.6%            0.0%            | 
|TERMINAL (d)       |        7/33 (21%)       5/22 (23%)       8/28 (29%)       5/22 (23%)       6/29 (21%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        693              573              616              715              686              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.211N         P=0.304          P=0.270          P=0.502N         P=0.412N         P=1.000N        | 
|POLY 3             |        P=0.030N*        P=0.567          P=0.390          P=0.237N         P=0.312N         P=0.057N        | 
|POLY 1.5           |        P=0.007N**       P=0.583          P=0.400          P=0.226N         P=0.301N         P=0.010N*       | 
|POLY 6             |        P=0.104N         P=0.535          P=0.369          P=0.262N         P=0.339N         P=0.270N        | 
|LOGISTIC REGRESSION|        P=0.058N         P=0.525          P=0.339          P=0.353N         P=0.381N         P=0.764N        | 
|COCH-ARM / FISHERS |        P<0.001N**       P=0.598N         P=0.405          P=0.207N         P=0.298N         P<0.001N**      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 5       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone: Femur                                                                                                                      | 
|     Osteopetrosis                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        12/50 (24%)      7/50 (14%)       9/50 (18%)       15/50 (30%)      14/50 (28%)      9/50 (18%)      | 
|POLY-3 RATE (b)    |        12/44.10         7/40.61          9/42.66          15/42.67         14/43.45         9/23.00         | 
|POLY-3 PERCENT (g) |        27.2%            17.2%            21.1%            35.2%            32.2%            39.1%           | 
|TERMINAL (d)       |        8/33 (24%)       3/22 (14%)       5/28 (18%)       9/22 (41%)       9/29 (31%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        498              600              616              552              587              461             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.399N         P=0.445N         P=0.097          P=0.303          P<0.001 **      | 
|POLY 3             |        P=0.073          P=0.199N         P=0.339N         P=0.284          P=0.389          P=0.250         | 
|POLY 1.5           |        P=0.239          P=0.177N         P=0.324N         P=0.296          P=0.403          P=0.528         | 
|POLY 6             |        P=0.018 *        P=0.242N         P=0.366N         P=0.260          P=0.363          P=0.059         | 
|LOGISTIC REGRESSION|        P=0.076          P=0.194N         P=0.329N         P=0.288          P=0.392          P=0.415         | 
|COCH-ARM / FISHERS |        P=0.441N         P=0.154N         P=0.312N         P=0.326          P=0.410          P=0.312N        | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain                                                                                                                            | 
|     Compression                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        9/50 (18%)       11/50 (22%)      15/50 (30%)      6/50 (12%)       12/50 (24%)      2/50 (4%)       | 
|POLY-3 RATE (b)    |        9/43.90          11/41.42         15/43.64         6/41.57          12/42.80         2/18.40         | 
|POLY-3 PERCENT (g) |        20.5%            26.6%            34.4%            14.4%            28.0%            10.9%           | 
|TERMINAL (d)       |        4/33 (12%)       7/22 (32%)       8/28 (29%)       2/22 (9%)        9/29 (31%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        545              520              518              664              570              552             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.129          P=0.171          P=0.081          P=0.497N         P=0.225          P=0.067         | 
|POLY 3             |        P=0.286N         P=0.342          P=0.109          P=0.326N         P=0.284          P=0.320N        | 
|POLY 1.5           |        P=0.081N         P=0.371          P=0.116          P=0.313N         P=0.301          P=0.124N        | 
|POLY 6             |        P=0.485          P=0.293          P=0.096          P=0.350N         P=0.251          P=0.584         | 
|LOGISTIC REGRESSION|        P=0.246N         P=0.357          P=0.114          P=0.313N         P=0.288          P=0.646N        | 
|COCH-ARM / FISHERS |        P=0.006N**       P=0.402          P=0.121          P=0.288N         P=0.312          P=0.026N*       | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 6       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain                                                                                                                            | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/50 (2%)        1/50 (2%)        0/50 (0%)        3/50 (6%)        0/50 (0%)        0/50 (0%)       | 
|POLY-3 RATE (b)    |        1/42.87          1/40.38          0/41.60          3/41.98          0/41.99          0/17.60         | 
|POLY-3 PERCENT (g) |        2.3%             2.5%             0.0%             7.2%             0.0%             0.0%            | 
|TERMINAL (d)       |        1/33 (3%)        0/22 (0%)        0/28 (0%)        0/22 (0%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        729 (T)          600              ---              561              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.600N         P=0.713          P=0.533N         P=0.274          P=0.526N         P=1.000N        | 
|POLY 3             |        P=0.311N         P=0.748          P=0.506N         P=0.297          P=0.504N         P=0.650N        | 
|POLY 1.5           |        P=0.281N         P=0.754          P=0.503N         P=0.299          P=0.501N         P=0.586N        | 
|POLY 6             |        P=0.390N         P=0.736          P=0.513N         P=0.292          P=0.511N         P=0.716N        | 
|LOGISTIC REGRESSION|        P=0.158N         P=0.759N         (e)              P=0.325          (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.230N         P=0.753N         P=0.500N         P=0.309          P=0.500N         P=0.500N        | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain                                                                                                                            | 
|     Hydrocephalus                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        3/50 (6%)        4/50 (8%)        8/50 (16%)       1/50 (2%)        10/50 (20%)      3/50 (6%)       | 
|POLY-3 RATE (b)    |        3/43.63          4/39.94          8/42.32          1/40.98          10/42.80         3/18.82         | 
|POLY-3 PERCENT (g) |        6.9%             10.0%            18.9%            2.4%             23.4%            15.9%           | 
|TERMINAL (d)       |        0/33 (0%)        4/22 (18%)       4/28 (14%)       0/22 (0%)        7/29 (24%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        545              729 (T)          591              678              570              552             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.330          P=0.076          P=0.374N         P=0.028 *        P=0.004 **      | 
|POLY 3             |        P=0.078          P=0.452          P=0.087          P=0.328N         P=0.030 *        P=0.289         | 
|POLY 1.5           |        P=0.266          P=0.475          P=0.093          P=0.320N         P=0.033 *        P=0.452         | 
|POLY 6             |        P=0.015 *        P=0.414          P=0.077          P=0.342N         P=0.025 *        P=0.148         | 
|LOGISTIC REGRESSION|        P=0.045 *        P=0.466          P=0.097          P=0.294N         P=0.036 *        P=0.374         | 
|COCH-ARM / FISHERS |        P=0.482N         P=0.500          P=0.100          P=0.309N         P=0.036 *        P=0.661N        | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 7       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Clitoral Gland                                                                                                                   | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/49 (10%)       2/49 (4%)        3/49 (6%)        1/48 (2%)        4/49 (8%)        3/50 (6%)       | 
|POLY-3 RATE (b)    |        5/42.09          2/39.53          3/41.12          1/40.25          4/41.85          3/19.08         | 
|POLY-3 PERCENT (g) |        11.9%            5.1%             7.3%             2.5%             9.6%             15.7%           | 
|TERMINAL (d)       |        4/33 (12%)       2/22 (9%)        3/28 (11%)       0/22 (0%)        2/29 (7%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        693              729 (T)          729 (T)          646              658              552             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.393N         P=0.448N         P=0.189N         P=0.581N         P<0.001 **      | 
|POLY 3             |        P=0.226          P=0.241N         P=0.368N         P=0.111N         P=0.504N         P=0.499         | 
|POLY 1.5           |        P=0.341          P=0.229N         P=0.361N         P=0.109N         P=0.499N         P=0.585N        | 
|POLY 6             |        P=0.213          P=0.265N         P=0.386N         P=0.116N         P=0.518N         P=0.266         | 
|LOGISTIC REGRESSION|        P=0.063          P=0.314N         P=0.413N         P=0.117N         P=0.526N         P=0.227         | 
|COCH-ARM / FISHERS |        P=0.573          P=0.218N         P=0.357N         P=0.107N         P=0.500N         P=0.346N        | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Clitoral Gland                                                                                                                   | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        3/49 (6%)        5/49 (10%)       4/49 (8%)        2/48 (4%)        2/49 (4%)        0/50 (0%)       | 
|POLY-3 RATE (b)    |        3/41.95          5/39.88          4/41.43          2/40.53          2/42.02          0/17.60         | 
|POLY-3 PERCENT (g) |        7.2%             12.5%            9.7%             4.9%             4.8%             0.0%            | 
|TERMINAL (d)       |        3/33 (9%)        3/22 (14%)       3/28 (11%)       0/22 (0%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        729 (T)          650              647              638              602              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.350N         P=0.182          P=0.423          P=0.607N         P=0.553N         P=1.000N        | 
|POLY 3             |        P=0.119N         P=0.328          P=0.493          P=0.516N         P=0.499N         P=0.336N        | 
|POLY 1.5           |        P=0.076N         P=0.342          P=0.498          P=0.514N         P=0.497N         P=0.215N        | 
|POLY 6             |        P=0.177N         P=0.303          P=0.481          P=0.524N         P=0.507N         P=0.511N        | 
|LOGISTIC REGRESSION|        P=0.117N         P=0.268          P=0.465          P=0.519N         P=0.503N         (e)             | 
|COCH-ARM / FISHERS |        P=0.031N*        P=0.357          P=0.500          P=0.510N         P=0.500N         P=0.117N        | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 8       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Clitoral Gland                                                                                                                   | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/49 (8%)        5/49 (10%)       4/49 (8%)        3/48 (6%)        4/49 (8%)        0/50 (0%)       | 
|POLY-3 RATE (b)    |        4/42.79          5/39.82          4/41.40          3/40.76          4/42.59          0/17.60         | 
|POLY-3 PERCENT (g) |        9.4%             12.6%            9.7%             7.4%             9.4%             0.0%            | 
|TERMINAL (d)       |        3/33 (9%)        4/22 (18%)       3/28 (11%)       0/22 (0%)        1/29 (3%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        393              650              654              646              576              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.483N         P=0.296          P=0.568          P=0.602N         P=0.599          P=0.508N        | 
|POLY 3             |        P=0.227N         P=0.455          P=0.626          P=0.527N         P=0.641          P=0.262N        | 
|POLY 1.5           |        P=0.115N         P=0.475          P=0.634          P=0.523N         P=0.643          P=0.141N        | 
|POLY 6             |        P=0.410N         P=0.422          P=0.611          P=0.536N         P=0.635          P=0.460N        | 
|LOGISTIC REGRESSION|        P=0.060N         P=0.491          P=0.643N         P=0.494N         P=0.629          P=0.072N        | 
|COCH-ARM / FISHERS |        P=0.033N*        P=0.500          P=0.643N         P=0.512N         P=0.643N         P=0.056N        | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Esophagus                                                                                                                        | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/48 (0%)        2/50 (4%)        0/48 (0%)        0/50 (0%)        0/49 (0%)        0/50 (0%)       | 
|POLY-3 RATE (b)    |        0/40.87          2/40.76          0/40.38          0/40.79          0/41.25          0/17.60         | 
|POLY-3 PERCENT (g) |        0.0%             4.9%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/31 (0%)        0/22 (0%)        0/27 (0%)        0/22 (0%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              612              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.731N         P=0.232          (e)              (e)              (e)              (e)             | 
|POLY 3             |        P=0.335N         P=0.236          (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        P=0.366N         P=0.241          (e)              (e)              (e)              (e)             | 
|POLY 6             |        P=0.372N         P=0.227          (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        P=0.294N         P=0.263          (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.389N         P=0.258          (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 9       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart                                                                                                                            | 
|     Cardiomyopathy                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        12/50 (24%)      15/50 (30%)      8/50 (16%)       13/50 (26%)      8/50 (16%)       6/50 (12%)      | 
|POLY-3 RATE (b)    |        12/43.15         15/42.04         8/42.59          13/42.47         8/42.25          6/20.84         | 
|POLY-3 PERCENT (g) |        27.8%            35.7%            18.8%            30.6%            18.9%            28.8%           | 
|TERMINAL (d)       |        11/33 (33%)      8/22 (36%)       6/28 (21%)       7/22 (32%)       7/29 (24%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        654              519              572              561              658              440             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.076          P=0.346N         P=0.188          P=0.321N         P<0.001 **      | 
|POLY 3             |        P=0.337N         P=0.290          P=0.230N         P=0.481          P=0.236N         P=0.578         | 
|POLY 1.5           |        P=0.178N         P=0.308          P=0.226N         P=0.482          P=0.228N         P=0.338N        | 
|POLY 6             |        P=0.484N         P=0.257          P=0.246N         P=0.472          P=0.260N         P=0.229         | 
|LOGISTIC REGRESSION|        P=0.540          P=0.232          P=0.264N         P=0.430          P=0.300N         P=0.176         | 
|COCH-ARM / FISHERS |        P=0.035N*        P=0.326          P=0.227N         P=0.500          P=0.227N         P=0.096N        | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        32/50 (64%)      32/50 (64%)      33/50 (66%)      30/50 (60%)      38/50 (76%)      28/50 (56%)     | 
|POLY-3 RATE (b)    |        32/46.45         32/44.61         33/46.14         30/42.81         38/47.48         28/34.74        | 
|POLY-3 PERCENT (g) |        68.9%            71.7%            71.5%            70.1%            80.0%            80.6%           | 
|TERMINAL (d)       |        24/33 (73%)      19/22 (86%)      21/28 (75%)      20/22 (91%)      24/29 (83%)      0/0 (0%)        | 
|FIRST INCIDENCE    |        393              407              437              561              463              350             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.055          P=0.234          P=0.096          P=0.072          P<0.001 **      | 
|POLY 3             |        P=0.089          P=0.471          P=0.479          P=0.545          P=0.147          P=0.153         | 
|POLY 1.5           |        P=0.334          P=0.526          P=0.495          P=0.565N         P=0.145          P=0.461         | 
|POLY 6             |        P=0.013 *        P=0.373          P=0.443          P=0.442          P=0.142          P=0.019 *       | 
|LOGISTIC REGRESSION|        P=0.028 *        P=0.507          P=0.482          P=0.508N         P=0.134          P=0.245         | 
|COCH-ARM / FISHERS |        P=0.239N         P=0.582N         P=0.500          P=0.418N         P=0.138          P=0.270N        | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 10      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Dilatation                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/50 (0%)        1/50 (2%)        2/50 (4%)        0/50 (0%)        2/50 (4%)        1/50 (2%)       | 
|POLY-3 RATE (b)    |        0/42.87          1/40.13          2/42.39          0/40.79          2/43.49          1/18.44         | 
|POLY-3 PERCENT (g) |        0.0%             2.5%             4.7%             0.0%             4.6%             5.4%            | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        1/28 (4%)        0/22 (0%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              679              437              ---              451              400             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.328          P=0.457          P=0.224          (e)              P=0.247          P=0.492         | 
|POLY 3             |        P=0.225          P=0.487          P=0.234          (e)              P=0.240          P=0.354         | 
|POLY 1.5           |        P=0.341          P=0.493          P=0.237          (e)              P=0.241          P=0.417         | 
|POLY 6             |        P=0.189          P=0.476          P=0.228          (e)              P=0.236          P=0.288         | 
|LOGISTIC REGRESSION|        P=0.328N         P=0.498          P=0.217          (e)              P=0.053          P=0.894         | 
|COCH-ARM / FISHERS |        P=0.533          P=0.500          P=0.247          (e)              P=0.247          P=0.500         | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Hyaline Droplet                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        33/50 (66%)      23/50 (46%)      30/50 (60%)      26/50 (52%)      26/50 (52%)      9/50 (18%)      | 
|POLY-3 RATE (b)    |        33/44.89         23/41.49         30/43.44         26/43.64         26/43.29         9/22.68         | 
|POLY-3 PERCENT (g) |        73.5%            55.4%            69.1%            59.6%            60.1%            39.7%           | 
|TERMINAL (d)       |        28/33 (85%)      19/22 (86%)      23/28 (82%)      17/22 (77%)      22/29 (76%)      0/0 (0%)        | 
|FIRST INCIDENCE    |        393              407              532              307              587              400             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.589          P=0.443          P=0.353          P=0.289N         P<0.001 **      | 
|POLY 3             |        P=0.023N*        P=0.048N*        P=0.403N         P=0.108N         P=0.115N         P=0.004N**      | 
|POLY 1.5           |        P<0.001N**       P=0.039N*        P=0.372N         P=0.115N         P=0.110N         P<0.001N**      | 
|POLY 6             |        P=0.219N         P=0.074N         P=0.461N         P=0.099N         P=0.134N         P=0.240N        | 
|LOGISTIC REGRESSION|        P=0.518          P=0.072N         P=0.424N         P=0.145N         P=0.126N         P=0.307N        | 
|COCH-ARM / FISHERS |        P<0.001N**       P=0.035N*        P=0.339N         P=0.111N         P=0.111N         P<0.001N**      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 11      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/50 (0%)        0/50 (0%)        0/50 (0%)        1/50 (2%)        1/50 (2%)        6/50 (12%)      | 
|POLY-3 RATE (b)    |        0/42.87          0/39.94          0/41.60          1/40.87          1/42.62          6/21.40         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             2.5%             2.4%             28.0%           | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        0/28 (0%)        0/22 (0%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              ---              707              524              405             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.455          P=0.513          P<0.001 **      | 
|POLY 3             |        P<0.001 **       (e)              (e)              P=0.490          P=0.499          P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P=0.494          P=0.500          P=0.004 **      | 
|POLY 6             |        P<0.001 **       (e)              (e)              P=0.484          P=0.494          P<0.001 **      | 
|LOGISTIC REGRESSION|        P=0.007 **       (e)              (e)              P=0.487          P=0.416          P=0.099         | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P=0.500          P=0.500          P=0.013 *       | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        38/50 (76%)      28/50 (56%)      31/50 (62%)      31/50 (62%)      41/50 (82%)      23/50 (46%)     | 
|POLY-3 RATE (b)    |        38/46.67         28/41.67         31/44.23         31/44.46         41/47.58         23/31.54        | 
|POLY-3 PERCENT (g) |        81.4%            67.2%            70.1%            69.7%            86.2%            72.9%           | 
|TERMINAL (d)       |        29/33 (88%)      21/22 (96%)      21/28 (75%)      18/22 (82%)      26/29 (90%)      0/0 (0%)        | 
|FIRST INCIDENCE    |        393              573              532              307              451              400             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.486          P=0.405N         P=0.322          P=0.132          P<0.001 **      | 
|POLY 3             |        P=0.336          P=0.077N         P=0.136N         P=0.129N         P=0.354          P=0.241N        | 
|POLY 1.5           |        P=0.330N         P=0.047N*        P=0.115N         P=0.121N         P=0.339          P=0.034N*       | 
|POLY 6             |        P=0.066          P=0.165N         P=0.178N         P=0.145N         P=0.363          P=0.482         | 
|LOGISTIC REGRESSION|        P=0.019 *        P=0.050N         P=0.102N         P=0.128N         P=0.312          P=0.561N        | 
|COCH-ARM / FISHERS |        P=0.024N*        P=0.028N*        P=0.097N         P=0.097N         P=0.312          P=0.002N**      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 12      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Transitional Epithelium                                                                                                  | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/50 (2%)        1/50 (2%)        1/50 (2%)        1/50 (2%)        0/50 (0%)        5/50 (10%)      | 
|POLY-3 RATE (b)    |        1/42.87          1/39.94          1/41.91          1/41.33          0/41.99          5/20.21         | 
|POLY-3 PERCENT (g) |        2.3%             2.5%             2.4%             2.4%             0.0%             24.7%           | 
|TERMINAL (d)       |        1/33 (3%)        1/22 (5%)        0/28 (0%)        0/22 (0%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        729 (T)          729 (T)          647              561              ---              516             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.669          P=0.742          P=0.719          P=0.526N         P<0.001 **      | 
|POLY 3             |        P=0.004 **       P=0.745          P=0.756          P=0.753          P=0.504N         P=0.015 *       | 
|POLY 1.5           |        P=0.004 **       P=0.752          P=0.759          P=0.755          P=0.501N         P=0.037 *       | 
|POLY 6             |        P=0.022 *        P=0.731          P=0.750          P=0.747          P=0.511N         P=0.005 **      | 
|LOGISTIC REGRESSION|        P=0.021 *        P=0.669          P=0.761          P=0.753N         (e)              P=0.027 *       | 
|COCH-ARM / FISHERS |        P=0.007 **       P=0.753N         P=0.753N         P=0.753N         P=0.500N         P=0.102         | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Angiectasis                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/50 (4%)        1/50 (2%)        2/50 (4%)        0/50 (0%)        5/50 (10%)       1/50 (2%)       | 
|POLY-3 RATE (b)    |        2/43.56          1/39.94          2/42.07          0/40.79          5/42.80          1/17.83         | 
|POLY-3 PERCENT (g) |        4.6%             2.5%             4.8%             0.0%             11.7%            5.6%            | 
|TERMINAL (d)       |        0/33 (0%)        1/22 (5%)        1/28 (4%)        0/22 (0%)        2/29 (7%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        611              729 (T)          591              ---              630              668             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.004 **       P=0.581N         P=0.661          P=0.246N         P=0.197          P=0.159         | 
|POLY 3             |        P=0.123          P=0.530N         P=0.682          P=0.252N         P=0.208          P=0.657         | 
|POLY 1.5           |        P=0.302          P=0.516N         P=0.689          P=0.246N         P=0.214          P=0.650N        | 
|POLY 6             |        P=0.039 *        P=0.555N         P=0.668          P=0.263N         P=0.196          P=0.490         | 
|LOGISTIC REGRESSION|        P=0.370          P=0.493N         P=0.694N         P=0.217N         P=0.216          P=0.844         | 
|COCH-ARM / FISHERS |        P=0.605          P=0.500N         P=0.691N         P=0.247N         P=0.218          P=0.500N        | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 13      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Basophilic Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        45/50 (90%)      46/50 (92%)      44/50 (88%)      42/50 (84%)      40/50 (80%)      20/50 (40%)     | 
|POLY-3 RATE (b)    |        45/48.80         46/47.73         44/48.32         42/46.37         40/46.94         20/30.51        | 
|POLY-3 PERCENT (g) |        92.2%            96.4%            91.1%            90.6%            85.2%            65.6%           | 
|TERMINAL (d)       |        31/33 (94%)      22/22 (100%)     26/28 (93%)      22/22 (100%)     26/29 (90%)      0/0 (0%)        | 
|FIRST INCIDENCE    |        437              407              444              252              451              407             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.020 *        P=0.284          P=0.083          P=0.512N         P<0.001 **      | 
|POLY 3             |        P<0.001N**       P=0.312          P=0.568N         P=0.536N         P=0.205N         P<0.001N**      | 
|POLY 1.5           |        P<0.001N**       P=0.387          P=0.534N         P=0.411N         P=0.159N         P<0.001N**      | 
|POLY 6             |        P=0.010N*        P=0.227          P=0.613N         P=0.639          P=0.298N         P=0.102N        | 
|LOGISTIC REGRESSION|        P<0.001N**       P=0.426          P=0.504N         P=0.358N         P=0.116N         P=0.002N**      | 
|COCH-ARM / FISHERS |        P<0.001N**       P=0.500          P=0.500N         P=0.277N         P=0.131N         P<0.001N**      | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Clear Cell Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        9/50 (18%)       8/50 (16%)       9/50 (18%)       13/50 (26%)      22/50 (44%)      2/50 (4%)       | 
|POLY-3 RATE (b)    |        9/43.47          8/40.81          9/42.52          13/41.33         22/43.03         2/19.24         | 
|POLY-3 PERCENT (g) |        20.7%            19.6%            21.2%            31.5%            51.1%            10.4%           | 
|TERMINAL (d)       |        7/33 (21%)       6/22 (27%)       7/28 (25%)       10/22 (46%)      19/29 (66%)      0/0 (0%)        | 
|FIRST INCIDENCE    |        640              600              572              646              576              393             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.413          P=0.477          P=0.051          P<0.001 **       P=0.281         | 
|POLY 3             |        P=0.103          P=0.558N         P=0.584          P=0.187          P=0.002 **       P=0.291N        | 
|POLY 1.5           |        P=0.488N         P=0.530N         P=0.596          P=0.203          P=0.003 **       P=0.113N        | 
|POLY 6             |        P<0.001 **       P=0.608N         P=0.557          P=0.159          P<0.001 **       P=0.609N        | 
|LOGISTIC REGRESSION|        P=0.074          P=0.586N         P=0.570          P=0.153          P=0.002 **       P=0.208N        | 
|COCH-ARM / FISHERS |        P=0.047N*        P=0.500N         P=0.602N         P=0.235          P=0.004 **       P=0.026N*       | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 14      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Eosinophilic Focus                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/50 (2%)        2/50 (4%)        6/50 (12%)       4/50 (8%)        12/50 (24%)      13/50 (26%)     | 
|POLY-3 RATE (b)    |        1/42.87          2/39.94          6/42.86          4/41.06          12/42.82         13/25.89        | 
|POLY-3 PERCENT (g) |        2.3%             5.0%             14.0%            9.7%             28.0%            50.2%           | 
|TERMINAL (d)       |        1/33 (3%)        2/22 (9%)        3/28 (11%)       2/22 (9%)        9/29 (31%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        729 (T)          729 (T)          571              678              587              393             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.359          P=0.046 *        P=0.099          P<0.001 **       P<0.001 **      | 
|POLY 3             |        P<0.001 **       P=0.475          P=0.055          P=0.165          P<0.001 **       P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       P=0.487          P=0.056          P=0.169          P<0.001 **       P<0.001 **      | 
|POLY 6             |        P<0.001 **       P=0.455          P=0.052          P=0.156          P<0.001 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        P<0.001 **       P=0.359          P=0.059          P=0.146          P<0.001 **       P=0.013 *       | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.500          P=0.056          P=0.181          P<0.001 **       P<0.001 **      | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/50 (4%)        1/50 (2%)        4/50 (8%)        0/50 (0%)        1/50 (2%)        3/50 (6%)       | 
|POLY-3 RATE (b)    |        2/43.66          1/40.77          4/42.65          0/40.79          1/41.99          3/19.82         | 
|POLY-3 PERCENT (g) |        4.6%             2.5%             9.4%             0.0%             2.4%             15.1%           | 
|TERMINAL (d)       |        1/33 (3%)        0/22 (0%)        1/28 (4%)        0/22 (0%)        1/29 (3%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        437              407              591              ---              729 (T)          447             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.042 *        P=0.549N         P=0.311          P=0.289N         P=0.528N         P=0.219         | 
|POLY 3             |        P=0.217          P=0.524N         P=0.326          P=0.252N         P=0.514N         P=0.205         | 
|POLY 1.5           |        P=0.247          P=0.512N         P=0.332          P=0.247N         P=0.506N         P=0.322         | 
|POLY 6             |        P=0.327          P=0.544N         P=0.317          P=0.261N         P=0.527N         P=0.108         | 
|LOGISTIC REGRESSION|        P=0.439N         P=0.434N         P=0.334          P=0.187N         P=0.515N         P=0.433N        | 
|COCH-ARM / FISHERS |        P=0.353          P=0.500N         P=0.339          P=0.247N         P=0.500N         P=0.500         | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 15      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/50 (0%)        0/50 (0%)        2/50 (4%)        0/50 (0%)        1/50 (2%)        7/50 (14%)      | 
|POLY-3 RATE (b)    |        0/42.87          0/39.94          2/42.28          0/40.79          1/42.62          7/22.18         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             4.7%             0.0%             2.4%             31.6%           | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        0/28 (0%)        0/22 (0%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              617              ---              524              393             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              P=0.226          (e)              P=0.513          P<0.001 **      | 
|POLY 3             |        P<0.001 **       (e)              P=0.234          (e)              P=0.499          P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       (e)              P=0.236          (e)              P=0.500          P<0.001 **      | 
|POLY 6             |        P<0.001 **       (e)              P=0.229          (e)              P=0.494          P<0.001 **      | 
|LOGISTIC REGRESSION|        P=0.010 *        (e)              P=0.236          (e)              P=0.416          P=0.075         | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              P=0.247          (e)              P=0.500          P=0.006 **      | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatodiaphragmatic Nodule                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        13/50 (26%)      8/50 (16%)       9/50 (18%)       6/50 (12%)       4/50 (8%)        5/50 (10%)      | 
|POLY-3 RATE (b)    |        13/44.34         8/41.50          9/43.56          6/41.12          4/42.44          5/21.21         | 
|POLY-3 PERCENT (g) |        29.3%            19.3%            20.7%            14.6%            9.4%             23.6%           | 
|TERMINAL (d)       |        9/33 (27%)       4/22 (18%)       6/28 (21%)       4/22 (18%)       2/29 (7%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        468              573              444              660              657              352             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.083          P=0.406N         P=0.344N         P=0.217N         P=0.034N*        P=0.046 *       | 
|POLY 3             |        P=0.231N         P=0.201N         P=0.244N         P=0.082N         P=0.017N*        P=0.431N        | 
|POLY 1.5           |        P=0.162N         P=0.183N         P=0.235N         P=0.074N         P=0.015N*        P=0.170N        | 
|POLY 6             |        P=0.245N         P=0.237N         P=0.269N         P=0.098N         P=0.021N*        P=0.388         | 
|LOGISTIC REGRESSION|        P=0.095N         P=0.179N         P=0.233N         P=0.075N         P=0.017N*        P=0.117N        | 
|COCH-ARM / FISHERS |        P=0.060N         P=0.163N         P=0.235N         P=0.062N         P=0.016N*        P=0.033N*       | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 16      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Infiltration Cellular Mixed Cell                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        9/50 (18%)       7/50 (14%)       9/50 (18%)       8/50 (16%)       15/50 (30%)      3/50 (6%)       | 
|POLY-3 RATE (b)    |        9/42.91          7/41.10          9/42.34          8/43.14          15/42.64         3/19.63         | 
|POLY-3 PERCENT (g) |        21.0%            17.0%            21.3%            18.5%            35.2%            15.3%           | 
|TERMINAL (d)       |        8/33 (24%)       3/22 (14%)       6/28 (21%)       4/22 (18%)       13/29 (45%)      0/0 (0%)        | 
|FIRST INCIDENCE    |        720              520              647              252              570              393             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.002 **       P=0.533          P=0.468          P=0.429          P=0.058          P=0.023 *       | 
|POLY 3             |        P=0.247          P=0.428N         P=0.592          P=0.495N         P=0.107          P=0.435N        | 
|POLY 1.5           |        P=0.465N         P=0.410N         P=0.600          P=0.494N         P=0.115          P=0.209N        | 
|POLY 6             |        P=0.039 *        P=0.461N         P=0.576          P=0.511N         P=0.090          P=0.473         | 
|LOGISTIC REGRESSION|        P=0.571N         P=0.482N         P=0.529          P=0.490N         P=0.066          P=0.714         | 
|COCH-ARM / FISHERS |        P=0.092N         P=0.393N         P=0.602N         P=0.500N         P=0.121          P=0.061N        | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Mixed Cell Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        8/50 (16%)       10/50 (20%)      10/50 (20%)      11/50 (22%)      23/50 (46%)      5/50 (10%)      | 
|POLY-3 RATE (b)    |        8/43.21          10/40.68         10/43.30         11/41.98         23/43.73         5/20.88         | 
|POLY-3 PERCENT (g) |        18.5%            24.6%            23.1%            26.2%            52.6%            24.0%           | 
|TERMINAL (d)       |        7/33 (21%)       8/22 (36%)       5/28 (18%)       4/22 (18%)       18/29 (62%)      0/0 (0%)        | 
|FIRST INCIDENCE    |        636              613              444              646              570              407             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.133          P=0.292          P=0.120          P<0.001 **       P=0.004 **      | 
|POLY 3             |        P=0.029 *        P=0.340          P=0.397          P=0.276          P<0.001 **       P=0.437         | 
|POLY 1.5           |        P=0.282          P=0.367          P=0.402          P=0.284          P<0.001 **       P=0.557N        | 
|POLY 6             |        P<0.001 **       P=0.295          P=0.383          P=0.263          P<0.001 **       P=0.180         | 
|LOGISTIC REGRESSION|        P=0.046 *        P=0.273          P=0.383          P=0.250          P<0.001 **       P=0.592         | 
|COCH-ARM / FISHERS |        P=0.219N         P=0.398          P=0.398          P=0.306          P<0.001 **       P=0.277N        | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 17      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Necrosis Focal                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/50 (8%)        2/50 (4%)        3/50 (6%)        4/50 (8%)        4/50 (8%)        15/50 (30%)     | 
|POLY-3 RATE (b)    |        4/44.16          2/40.27          3/42.40          4/41.32          4/43.17          15/27.82        | 
|POLY-3 PERCENT (g) |        9.1%             5.0%             7.1%             9.7%             9.3%             53.9%           | 
|TERMINAL (d)       |        0/33 (0%)        1/22 (5%)        1/28 (4%)        0/22 (0%)        1/29 (3%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        545              638              572              638              524              393             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.426N         P=0.544N         P=0.556          P=0.601          P<0.001 **      | 
|POLY 3             |        P<0.001 **       P=0.380N         P=0.522N         P=0.607          P=0.631          P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       P=0.360N         P=0.510N         P=0.620          P=0.639          P<0.001 **      | 
|POLY 6             |        P<0.001 **       P=0.415N         P=0.544N         P=0.584          P=0.613          P<0.001 **      | 
|LOGISTIC REGRESSION|        P=0.005 **       P=0.316N         P=0.498N         P=0.635N         P=0.631          P=0.283         | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.339N         P=0.500N         P=0.643N         P=0.643N         P=0.005 **      | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Bile Duct                                                                                                                 | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/50 (4%)        1/50 (2%)        4/50 (8%)        4/50 (8%)        3/50 (6%)        10/50 (20%)     | 
|POLY-3 RATE (b)    |        2/42.87          1/40.16          4/43.05          4/41.72          3/42.74          10/23.86        | 
|POLY-3 PERCENT (g) |        4.7%             2.5%             9.3%             9.6%             7.0%             41.9%           | 
|TERMINAL (d)       |        2/33 (6%)        0/22 (0%)        1/28 (4%)        1/22 (5%)        1/29 (3%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        729 (T)          672              444              561              524              400             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.616N         P=0.299          P=0.241          P=0.457          P<0.001 **      | 
|POLY 3             |        P<0.001 **       P=0.523N         P=0.338          P=0.324          P=0.499          P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       P=0.512N         P=0.341          P=0.327          P=0.502          P=0.002 **      | 
|POLY 6             |        P<0.001 **       P=0.541N         P=0.330          P=0.315          P=0.489          P<0.001 **      | 
|LOGISTIC REGRESSION|        P=0.026 *        P=0.545N         P=0.338          P=0.329          P=0.500          P=0.045 *       | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.500N         P=0.339          P=0.339          P=0.500          P=0.014 *       | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 18      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Cytomegaly                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/50 (0%)        0/50 (0%)        7/50 (14%)       23/50 (46%)      32/50 (64%)      29/50 (58%)     | 
|POLY-3 RATE (b)    |        0/42.87          0/39.94          7/42.54          23/42.07         32/45.36         29/36.57        | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             16.5%            54.7%            70.5%            79.3%           | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        4/28 (14%)       16/22 (73%)      24/29 (83%)      0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              572              650              451              350             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              P=0.007 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 3             |        P<0.001 **       (e)              P=0.007 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       (e)              P=0.007 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 6             |        P<0.001 **       (e)              P=0.006 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        P<0.001 **       (e)              P=0.009 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              P=0.006 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Hyperplasia Regenerative                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/50 (0%)        0/50 (0%)        0/50 (0%)        0/50 (0%)        8/50 (16%)       50/50 (100%)    | 
|POLY-3 RATE (b)    |        0/42.87          0/39.94          0/41.60          0/40.79          8/42.53          50/50.00        | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             18.8%            100.0%          | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        0/28 (0%)        0/22 (0%)        6/29 (21%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              656              350             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              (e)              P=0.003 **       P<0.001 **      | 
|POLY 3             |        P<0.001 **       (e)              (e)              (e)              P=0.003 **       P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              (e)              P=0.004 **       P<0.001 **      | 
|POLY 6             |        P<0.001 **       (e)              (e)              (e)              P=0.003 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        P<0.001 **       (e)              (e)              (e)              P=0.004 **       P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              (e)              P=0.003 **       P<0.001 **      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 19      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Vacuolization Cytoplasmic                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/50 (8%)        5/50 (10%)       7/50 (14%)       4/50 (8%)        3/50 (6%)        5/50 (10%)      | 
|POLY-3 RATE (b)    |        4/43.89          5/41.01          7/43.76          4/41.57          3/42.62          5/20.97         | 
|POLY-3 PERCENT (g) |        9.1%             12.2%            16.0%            9.6%             7.0%             23.9%           | 
|TERMINAL (d)       |        1/33 (3%)        1/22 (5%)        2/28 (7%)        0/22 (0%)        2/29 (7%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        393              573              437              651              524              460             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.006 **       P=0.361          P=0.228          P=0.527          P=0.550N         P=0.031 *       | 
|POLY 3             |        P=0.299          P=0.457          P=0.258          P=0.614          P=0.516N         P=0.137         | 
|POLY 1.5           |        P=0.401          P=0.476          P=0.261          P=0.622          P=0.507N         P=0.269         | 
|POLY 6             |        P=0.310          P=0.428          P=0.249          P=0.600          P=0.535N         P=0.049 *       | 
|LOGISTIC REGRESSION|        P=0.274N         P=0.525          P=0.258          P=0.626N         P=0.510N         P=0.529N        | 
|COCH-ARM / FISHERS |        P=0.529N         P=0.500          P=0.262          P=0.643N         P=0.500N         P=0.500         | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Kupffer Cell                                                                                                              | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/50 (0%)        2/50 (4%)        3/50 (6%)        2/50 (4%)        6/50 (12%)       4/50 (8%)       | 
|POLY-3 RATE (b)    |        0/42.87          2/40.76          3/42.41          2/42.26          6/44.30          4/20.52         | 
|POLY-3 PERCENT (g) |        0.0%             4.9%             7.1%             4.7%             13.5%            19.5%           | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        0/28 (0%)        0/22 (0%)        1/29 (3%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              573              562              307              463              459             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.221          P=0.113          P=0.238          P=0.018 *        P=0.031 *       | 
|POLY 3             |        P=0.005 **       P=0.226          P=0.116          P=0.234          P=0.017 *        P=0.013 *       | 
|POLY 1.5           |        P=0.022 *        P=0.231          P=0.118          P=0.235          P=0.017 *        P=0.026 *       | 
|POLY 6             |        P=0.002 **       P=0.216          P=0.112          P=0.229          P=0.016 *        P=0.006 **      | 
|LOGISTIC REGRESSION|        P=0.543N         P=0.258          P=0.121          P=0.396          P=0.011 *        P=0.359         | 
|COCH-ARM / FISHERS |        P=0.104          P=0.247          P=0.121          P=0.247          P=0.013 *        P=0.059         | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 20      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Congestion                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/50 (8%)        7/50 (14%)       2/50 (4%)        8/50 (16%)       1/50 (2%)        1/50 (2%)       | 
|POLY-3 RATE (b)    |        4/44.42          7/42.43          2/42.54          8/42.96          1/41.99          1/18.32         | 
|POLY-3 PERCENT (g) |        9.0%             16.5%            4.7%             18.6%            2.4%             5.5%            | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        0/28 (0%)        0/22 (0%)        1/29 (3%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        468              519              444              293              729 (T)          478             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.373N         P=0.209          P=0.370N         P=0.144          P=0.203N         P=0.705         | 
|POLY 3             |        P=0.125N         P=0.234          P=0.357N         P=0.159          P=0.196N         P=0.514N        | 
|POLY 1.5           |        P=0.082N         P=0.247          P=0.346N         P=0.166          P=0.187N         P=0.346N        | 
|POLY 6             |        P=0.160N         P=0.212          P=0.378N         P=0.147          P=0.213N         P=0.597         | 
|LOGISTIC REGRESSION|        P=0.003N**       P=0.310          P=0.348N         P=0.218          P=0.187N         P=0.058N        | 
|COCH-ARM / FISHERS |        P=0.032N*        P=0.262          P=0.339N         P=0.178          P=0.181N         P=0.181N        | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Edema                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/50 (0%)        0/50 (0%)        0/50 (0%)        0/50 (0%)        1/50 (2%)        2/50 (4%)       | 
|POLY-3 RATE (b)    |        0/42.87          0/39.94          0/41.60          0/40.79          1/42.62          2/19.23         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             2.4%             10.4%           | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        0/28 (0%)        0/22 (0%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              524              405             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.009 **       (e)              (e)              (e)              P=0.513          P=0.221         | 
|POLY 3             |        P=0.005 **       (e)              (e)              (e)              P=0.499          P=0.115         | 
|POLY 1.5           |        P=0.008 **       (e)              (e)              (e)              P=0.500          P=0.160         | 
|POLY 6             |        P=0.014 *        (e)              (e)              (e)              P=0.494          P=0.080         | 
|LOGISTIC REGRESSION|        P=0.214          (e)              (e)              (e)              P=0.416          P=0.706         | 
|COCH-ARM / FISHERS |        P=0.020 *        (e)              (e)              (e)              P=0.500          P=0.247         | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 21      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/50 (8%)        7/50 (14%)       1/50 (2%)        3/50 (6%)        5/50 (10%)       19/50 (38%)     | 
|POLY-3 RATE (b)    |        4/44.66          7/42.41          1/41.87          3/41.59          5/43.43          19/29.60        | 
|POLY-3 PERCENT (g) |        9.0%             16.5%            2.4%             7.2%             11.5%            64.2%           | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        0/28 (0%)        0/22 (0%)        1/29 (3%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        468              573              658              642              524              350             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.229          P=0.204N         P=0.514N         P=0.479          P<0.001 **      | 
|POLY 3             |        P<0.001 **       P=0.231          P=0.198N         P=0.539N         P=0.482          P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       P=0.244          P=0.189N         P=0.525N         P=0.493          P<0.001 **      | 
|POLY 6             |        P<0.001 **       P=0.211          P=0.215N         P=0.561N         P=0.462          P<0.001 **      | 
|LOGISTIC REGRESSION|        P<0.001 **       P=0.310          P=0.182N         P=0.441N         P=0.469          P=0.046 *       | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.262          P=0.181N         P=0.500N         P=0.500          P<0.001 **      | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Infiltration Cellular Histiocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        45/50 (90%)      41/50 (82%)      47/50 (94%)      44/50 (88%)      49/50 (98%)      42/50 (84%)     | 
|POLY-3 RATE (b)    |        45/48.81         41/46.78         47/48.64         44/45.77         49/49.65         42/44.19        | 
|POLY-3 PERCENT (g) |        92.2%            87.7%            96.6%            96.1%            98.7%            95.0%           | 
|TERMINAL (d)       |        32/33 (97%)      22/22 (100%)     28/28 (100%)     22/22 (100%)     29/29 (100%)     0/0 (0%)        | 
|FIRST INCIDENCE    |        393              407              437              552              451              350             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.094          P=0.123          P=0.037 *        P=0.099          P<0.001 **      | 
|POLY 3             |        P=0.245          P=0.329N         P=0.277          P=0.332          P=0.112          P=0.434         | 
|POLY 1.5           |        P=0.496          P=0.276N         P=0.311          P=0.449          P=0.106          P=0.654N        | 
|POLY 6             |        P=0.094          P=0.386N         P=0.243          P=0.284          P=0.133          P=0.236         | 
|LOGISTIC REGRESSION|        P=0.027 *        P=0.234N         P=0.353          P=0.625          P=0.104          P=0.498         | 
|COCH-ARM / FISHERS |        P=0.313N         P=0.194N         P=0.357          P=0.500N         P=0.102          P=0.277N        | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 22      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Metaplasia Osseous                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/50 (0%)        2/50 (4%)        0/50 (0%)        0/50 (0%)        0/50 (0%)        0/50 (0%)       | 
|POLY-3 RATE (b)    |        0/42.87          2/40.70          0/41.60          0/40.79          0/41.99          0/17.60         | 
|POLY-3 PERCENT (g) |        0.0%             4.9%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        0/28 (0%)        0/22 (0%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              520              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.608N         P=0.214          (e)              (e)              (e)              (e)             | 
|POLY 3             |        P=0.337N         P=0.225          (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        P=0.369N         P=0.231          (e)              (e)              (e)              (e)             | 
|POLY 6             |        P=0.376N         P=0.215          (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        P=0.293N         P=0.258          (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.393N         P=0.247          (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolar Epithelium                                                                                                        | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/50 (10%)       4/50 (8%)        10/50 (20%)      5/50 (10%)       5/50 (10%)       7/50 (14%)      | 
|POLY-3 RATE (b)    |        5/42.87          4/40.29          10/42.37         5/40.79          5/41.99          7/21.20         | 
|POLY-3 PERCENT (g) |        11.7%            9.9%             23.6%            12.3%            11.9%            33.0%           | 
|TERMINAL (d)       |        5/33 (15%)       3/22 (14%)       8/28 (29%)       5/22 (23%)       5/29 (17%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        729 (T)          631              591              729 (T)          729 (T)          459             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.554          P=0.074          P=0.362          P=0.548          P<0.001 **      | 
|POLY 3             |        P=0.114          P=0.539N         P=0.120          P=0.599          P=0.618          P=0.057         | 
|POLY 1.5           |        P=0.200          P=0.520N         P=0.126          P=0.610          P=0.627          P=0.154         | 
|POLY 6             |        P=0.095          P=0.571N         P=0.110          P=0.578          P=0.598          P=0.013 *       | 
|LOGISTIC REGRESSION|        P=0.004 **       P=0.619N         P=0.098          P=0.362          P=0.548          P=0.017 *       | 
|COCH-ARM / FISHERS |        P=0.431          P=0.500N         P=0.131          P=0.630N         P=0.630N         P=0.380         | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 23      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Ectasia                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/50 (0%)        0/49 (0%)        0/48 (0%)        3/50 (6%)        0/50 (0%)        0/50 (0%)       | 
|POLY-3 RATE (b)    |        0/42.87          0/39.58          0/40.38          3/41.07          0/41.99          0/17.60         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             7.3%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        0/27 (0%)        2/22 (9%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              ---              651              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.919N         (e)              (e)              P=0.078          (e)              (e)             | 
|POLY 3             |        P=0.543N         (e)              (e)              P=0.111          (e)              (e)             | 
|POLY 1.5           |        P=0.492N         (e)              (e)              P=0.113          (e)              (e)             | 
|POLY 6             |        P=0.686N         (e)              (e)              P=0.106          (e)              (e)             | 
|LOGISTIC REGRESSION|        P=0.763N         (e)              (e)              P=0.110          (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.430N         (e)              (e)              P=0.121          (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/50 (4%)        3/49 (6%)        1/48 (2%)        5/50 (10%)       5/50 (10%)       0/50 (0%)       | 
|POLY-3 RATE (b)    |        2/42.87          3/39.89          1/40.38          5/40.89          5/42.27          0/17.60         | 
|POLY-3 PERCENT (g) |        4.7%             7.5%             2.5%             12.2%            11.8%            0.0%            | 
|TERMINAL (d)       |        2/33 (6%)        2/22 (9%)        1/27 (4%)        3/22 (14%)       4/29 (14%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        729 (T)          644              729 (T)          715              654              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.268          P=0.343          P=0.570N         P=0.094          P=0.174          P=1.000N        | 
|POLY 3             |        P=0.460          P=0.467          P=0.521N         P=0.196          P=0.209          P=0.457N        | 
|POLY 1.5           |        P=0.401N         P=0.479          P=0.516N         P=0.203          P=0.215          P=0.349N        | 
|POLY 6             |        P=0.179          P=0.446          P=0.532N         P=0.183          P=0.197          P=0.589N        | 
|LOGISTIC REGRESSION|        P=0.382          P=0.435          P=0.570N         P=0.124          P=0.183          (e)             | 
|COCH-ARM / FISHERS |        P=0.154N         P=0.490          P=0.515N         P=0.218          P=0.218          P=0.247N        | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 24      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/50 (10%)       2/49 (4%)        2/48 (4%)        11/50 (22%)      3/50 (6%)        0/50 (0%)       | 
|POLY-3 RATE (b)    |        5/42.87          2/39.77          2/40.44          11/41.92         3/42.48          0/17.60         | 
|POLY-3 PERCENT (g) |        11.7%            5.0%             5.0%             26.2%            7.1%             0.0%            | 
|TERMINAL (d)       |        5/33 (15%)       1/22 (5%)        1/27 (4%)        5/22 (23%)       2/29 (7%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        729 (T)          679              715              638              581              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.652N         P=0.391N         P=0.299N         P=0.023 *        P=0.418N         P=1.000N        | 
|POLY 3             |        P=0.221N         P=0.246N         P=0.239N         P=0.072          P=0.361N         P=0.203N        | 
|POLY 1.5           |        P=0.100N         P=0.236N         P=0.234N         P=0.075          P=0.356N         P=0.093N        | 
|POLY 6             |        P=0.441N         P=0.267N         P=0.252N         P=0.067          P=0.374N         P=0.416N        | 
|LOGISTIC REGRESSION|        P=0.320N         P=0.312N         P=0.290N         P=0.060          P=0.380N         (e)             | 
|COCH-ARM / FISHERS |        P=0.026N*        P=0.226N         P=0.235N         P=0.086          P=0.357N         P=0.028N*       | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mediastinal                                                                                                          | 
|     Congestion                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/50 (8%)        3/50 (6%)        3/50 (6%)        3/50 (6%)        1/50 (2%)        9/50 (18%)      | 
|POLY-3 RATE (b)    |        4/42.87          3/40.88          3/42.54          3/41.79          1/42.15          9/23.79         | 
|POLY-3 PERCENT (g) |        9.3%             7.3%             7.1%             7.2%             2.4%             37.8%           | 
|TERMINAL (d)       |        4/33 (12%)       0/22 (0%)        1/28 (4%)        0/22 (0%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        729 (T)          636              444              552              686              393             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.650N         P=0.571N         P=0.641N         P=0.221N         P<0.001 **      | 
|POLY 3             |        P=0.003 **       P=0.526N         P=0.504N         P=0.514N         P=0.183N         P=0.008 **      | 
|POLY 1.5           |        P=0.004 **       P=0.514N         P=0.500N         P=0.511N         P=0.180N         P=0.030 *       | 
|POLY 6             |        P=0.005 **       P=0.547N         P=0.517N         P=0.524N         P=0.191N         P<0.001 **      | 
|LOGISTIC REGRESSION|        P=0.140          P=0.526N         P=0.501N         P=0.511N         P=0.206N         P=0.248         | 
|COCH-ARM / FISHERS |        P=0.011 *        P=0.500N         P=0.500N         P=0.500N         P=0.181N         P=0.117         | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 25      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mediastinal                                                                                                          | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/50 (10%)       8/50 (16%)       9/50 (18%)       5/50 (10%)       7/50 (14%)       25/50 (50%)     | 
|POLY-3 RATE (b)    |        5/44.55          8/40.81          9/42.41          5/40.87          7/42.46          25/32.79        | 
|POLY-3 PERCENT (g) |        11.2%            19.6%            21.2%            12.2%            16.5%            76.3%           | 
|TERMINAL (d)       |        1/33 (3%)        5/22 (23%)       6/28 (21%)       4/22 (18%)       6/29 (21%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        483              613              591              707              590              405             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.153          P=0.147          P=0.478          P=0.320          P<0.001 **      | 
|POLY 3             |        P<0.001 **       P=0.219          P=0.163          P=0.575          P=0.345          P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       P=0.244          P=0.178          P=0.596          P=0.363          P<0.001 **      | 
|POLY 6             |        P<0.001 **       P=0.182          P=0.141          P=0.540          P=0.311          P<0.001 **      | 
|LOGISTIC REGRESSION|        P<0.001 **       P=0.280          P=0.195          P=0.630          P=0.380          P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.277          P=0.194          P=0.630N         P=0.380          P<0.001 **      | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mediastinal                                                                                                          | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        23/50 (46%)      22/50 (44%)      32/50 (64%)      15/50 (30%)      16/50 (32%)      31/50 (62%)     | 
|POLY-3 RATE (b)    |        23/47.15         22/43.02         32/45.35         15/42.50         16/44.30         31/37.24        | 
|POLY-3 PERCENT (g) |        48.8%            51.1%            70.6%            35.3%            36.1%            83.3%           | 
|TERMINAL (d)       |        12/33 (36%)      12/22 (55%)      22/28 (79%)      8/22 (36%)       9/29 (31%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        393              573              444              552              570              405             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.230          P=0.029 *        P=0.363N         P=0.236N         P<0.001 **      | 
|POLY 3             |        P=0.003 **       P=0.495          P=0.022 *        P=0.137N         P=0.152N         P<0.001 **      | 
|POLY 1.5           |        P=0.012 *        P=0.562          P=0.033 *        P=0.112N         P=0.131N         P=0.005 **      | 
|POLY 6             |        P<0.001 **       P=0.407          P=0.012 *        P=0.181N         P=0.190N         P<0.001 **      | 
|LOGISTIC REGRESSION|        P=0.026 *        P=0.515N         P=0.053          P=0.078N         P=0.108N         P=0.300         | 
|COCH-ARM / FISHERS |        P=0.067          P=0.500N         P=0.054          P=0.074N         P=0.109N         P=0.080         | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 26      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/50 (2%)        2/50 (4%)        3/50 (6%)        4/47 (9%)        0/49 (0%)        6/49 (12%)      | 
|POLY-3 RATE (b)    |        1/43.28          2/40.35          3/42.35          4/40.25          0/40.99          6/21.44         | 
|POLY-3 PERCENT (g) |        2.3%             5.0%             7.1%             9.9%             0.0%             28.0%           | 
|TERMINAL (d)       |        0/33 (0%)        1/22 (5%)        1/28 (4%)        2/22 (9%)        0/28 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        611              613              591              618              ---              405             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.440          P=0.279          P=0.138          P=0.514N         P=0.002 **      | 
|POLY 3             |        P=0.021 *        P=0.475          P=0.297          P=0.156          P=0.511N         P=0.006 **      | 
|POLY 1.5           |        P=0.025 *        P=0.487          P=0.302          P=0.158          P=0.507N         P=0.016 *       | 
|POLY 6             |        P=0.041 *        P=0.455          P=0.287          P=0.151          P=0.519N         P<0.001 **      | 
|LOGISTIC REGRESSION|        P=0.237          P=0.515          P=0.306          P=0.163          P=0.520N         P=0.319         | 
|COCH-ARM / FISHERS |        P=0.050          P=0.500          P=0.309          P=0.162          P=0.505N         P=0.053         | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        3/50 (6%)        1/50 (2%)        2/50 (4%)        2/47 (4%)        3/49 (6%)        2/49 (4%)       | 
|POLY-3 RATE (b)    |        3/43.28          1/39.94          2/41.60          2/39.99          3/40.99          2/18.48         | 
|POLY-3 PERCENT (g) |        6.9%             2.5%             4.8%             5.0%             7.3%             10.8%           | 
|TERMINAL (d)       |        2/33 (6%)        1/22 (5%)        2/28 (7%)        1/22 (5%)        3/28 (11%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        611              729 (T)          729 (T)          618              729 (T)          447             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.003 **       P=0.426N         P=0.566N         P=0.604N         P=0.592          P=0.059         | 
|POLY 3             |        P=0.233          P=0.334N         P=0.518N         P=0.536N         P=0.638          P=0.499         | 
|POLY 1.5           |        P=0.358          P=0.320N         P=0.508N         P=0.533N         P=0.647          P=0.658         | 
|POLY 6             |        P=0.194          P=0.359N         P=0.536N         P=0.546N         P=0.618          P=0.310         | 
|LOGISTIC REGRESSION|        P=0.193          P=0.330N         P=0.518N         P=0.529N         P=0.632          P=0.694         | 
|COCH-ARM / FISHERS |        P=0.577          P=0.309N         P=0.500N         P=0.530N         P=0.651          P=0.510N        | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 27      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node: Pancreatic                                                                                                           | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/26 (0%)        0/24 (0%)        0/36 (0%)        0/19 (0%)        0/21 (0%)        2/40 (5%)       | 
|POLY-3 RATE (b)    |        0/21.36          0/20.27          0/31.39          0/16.17          0/17.48          2/16.18         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             12.4%           | 
|TERMINAL (d)       |        0/14 (0%)        0/13 (0%)        0/23 (0%)        0/9 (0%)         0/12 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              352             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.005 **       (e)              (e)              (e)              (e)              P=0.189         | 
|POLY 3             |        P=0.014 *        (e)              (e)              (e)              (e)              P=0.182         | 
|POLY 1.5           |        P=0.019 *        (e)              (e)              (e)              (e)              P=0.248         | 
|POLY 6             |        P=0.043 *        (e)              (e)              (e)              (e)              P=0.118         | 
|LOGISTIC REGRESSION|        P=0.435          (e)              (e)              (e)              (e)              P=0.664         | 
|COCH-ARM / FISHERS |        P=0.032 *        (e)              (e)              (e)              (e)              P=0.364         | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node: Pancreatic                                                                                                           | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/26 (0%)        1/24 (4%)        2/36 (6%)        0/19 (0%)        4/21 (19%)       1/40 (3%)       | 
|POLY-3 RATE (b)    |        0/21.36          1/20.27          2/31.87          0/16.17          4/17.65          1/15.29         | 
|POLY-3 PERCENT (g) |        0.0%             4.9%             6.3%             0.0%             22.7%            6.5%            | 
|TERMINAL (d)       |        0/14 (0%)        1/13 (8%)        0/23 (0%)        0/9 (0%)         3/12 (25%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              729 (T)          654              ---              686              472             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.003 **       P=0.485          P=0.219          (e)              P=0.044 *        P=0.410         | 
|POLY 3             |        P=0.116          P=0.490          P=0.330          (e)              P=0.030 *        P=0.436         | 
|POLY 1.5           |        P=0.321          P=0.489          P=0.323          (e)              P=0.031 *        P=0.508         | 
|POLY 6             |        P=0.017 *        P=0.486          P=0.338          (e)              P=0.029 *        P=0.345         | 
|LOGISTIC REGRESSION|        P=0.296          P=0.485          P=0.297          (e)              P=0.033 *        P=0.819         | 
|COCH-ARM / FISHERS |        P=0.609N         P=0.480          P=0.333          (e)              P=0.034 *        P=0.606         | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 28      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node: Renal                                                                                                                | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/26 (0%)        0/24 (0%)        2/36 (6%)        0/19 (0%)        2/21 (10%)       1/40 (3%)       | 
|POLY-3 RATE (b)    |        0/21.36          0/20.27          2/31.44          0/16.17          2/18.13          1/15.39         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             6.4%             0.0%             11.0%            6.5%            | 
|TERMINAL (d)       |        0/14 (0%)        0/13 (0%)        1/23 (4%)        0/9 (0%)         0/12 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              715              ---              587              407             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.046 *        (e)              P=0.278          (e)              P=0.227          P=0.483         | 
|POLY 3             |        P=0.180          (e)              P=0.326          (e)              P=0.196          P=0.438         | 
|POLY 1.5           |        P=0.334          (e)              P=0.321          (e)              P=0.193          P=0.509         | 
|POLY 6             |        P=0.090          (e)              P=0.332          (e)              P=0.199          P=0.346         | 
|LOGISTIC REGRESSION|        P=0.679          (e)              P=0.334          (e)              P=0.175          P=0.851         | 
|COCH-ARM / FISHERS |        P=0.555          (e)              P=0.333          (e)              P=0.194          P=0.606         | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        48/50 (96%)      46/50 (92%)      46/50 (92%)      45/50 (90%)      44/49 (90%)      43/49 (88%)     | 
|POLY-3 RATE (b)    |        48/49.22         46/47.77         46/48.31         45/46.59         44/48.22         43/44.25        | 
|POLY-3 PERCENT (g) |        97.5%            96.3%            95.2%            96.6%            91.2%            97.2%           | 
|TERMINAL (d)       |        33/33 (100%)     22/22 (100%)     27/28 (96%)      22/22 (100%)     26/29 (90%)      0/0 (0%)        | 
|FIRST INCIDENCE    |        393              407              437              451              451              350             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.046 *        P=0.320          P=0.077          P=0.535          P<0.001 **      | 
|POLY 3             |        P=0.612N         P=0.613N         P=0.468N         P=0.654N         P=0.165N         P=0.771N        | 
|POLY 1.5           |        P=0.398N         P=0.483N         P=0.400N         P=0.502N         P=0.176N         P=0.405N        | 
|POLY 6             |        P=0.522          P=0.804N         P=0.573N         P=0.786N         P=0.169N         P=0.686         | 
|LOGISTIC REGRESSION|        P=0.082          P=0.394N         P=0.311N         P=0.361N         P=0.203N         P=0.494         | 
|COCH-ARM / FISHERS |        P=0.165N         P=0.339N         P=0.339N         P=0.218N         P=0.210N         P=0.128N        | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 29      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mesentery                                                                                                                        | 
|     Accessory Spleen                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/10 (20%)       0/10 (0%)        1/18 (6%)        2/14 (14%)       1/13 (8%)        0/5 (0%)        | 
|POLY-3 RATE (b)    |        2/9.48           0/8.66           1/15.81          2/12.97          1/9.97           0/2.17          | 
|POLY-3 PERCENT (g) |        21.1%            0.0%             6.3%             15.4%            10.0%            0.0%            | 
|TERMINAL (d)       |        2/7 (29%)        0/6 (0%)         1/11 (9%)        1/8 (13%)        1/5 (20%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        729 (T)          ---              729 (T)          638              729 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.838          P=0.265N         P=0.337N         P=0.659N         P=0.627N         P=1.000N        | 
|POLY 3             |        P=0.530N         P=0.246N         P=0.317N         P=0.581N         P=0.482N         P=0.576N        | 
|POLY 1.5           |        P=0.503N         P=0.237N         P=0.307N         P=0.575N         P=0.448N         P=0.497N        | 
|POLY 6             |        P=0.625          P=0.262N         P=0.328N         P=0.592N         P=0.531N         P=0.670N        | 
|LOGISTIC REGRESSION|        P=0.849N         (e)              P=0.337N         P=0.569N         P=0.627N         (e)             | 
|COCH-ARM / FISHERS |        P=0.449N         P=0.237N         P=0.284N         P=0.563N         P=0.398N         P=0.429N        | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mesentery: Fat                                                                                                                   | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        8/10 (80%)       10/10 (100%)     18/18 (100%)     12/14 (86%)      9/13 (69%)       3/5 (60%)       | 
|POLY-3 RATE (b)    |        8/10.00          10/10.00         18/18.00         12/14.00         9/12.56          3/3.87          | 
|POLY-3 PERCENT (g) |        80.0%            100.0%           100.0%           85.7%            71.6%            77.6%           | 
|TERMINAL (d)       |        5/7 (71%)        6/6 (100%)       11/11 (100%)     6/8 (75%)        2/5 (40%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        611              573              518              638              463              522             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.033 *        P=0.194          P=0.044 *        P=0.198          P=0.339          P=0.007 **      | 
|POLY 3             |        P=0.113N         P=0.227          P=0.106          P=0.571          P=0.513N         P=0.727N        | 
|POLY 1.5           |        P=0.055N         P=0.227          P=0.106          P=0.571          P=0.490N         P=0.595N        | 
|POLY 6             |        P=0.224N         P=0.227          P=0.106          P=0.571          P=0.546N         P=0.659         | 
|LOGISTIC REGRESSION|        P=0.006N**       (e)              (e)              (e)              P=0.278N         P=0.780N        | 
|COCH-ARM / FISHERS |        P=0.020N*        P=0.237          P=0.119          P=0.563          P=0.463N         P=0.407N        | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 30      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose                                                                                                                             | 
|     Foreign Body                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/50 (4%)        0/50 (0%)        1/50 (2%)        1/49 (2%)        0/50 (0%)        1/50 (2%)       | 
|POLY-3 RATE (b)    |        2/43.61          0/39.94          1/41.91          1/41.28          0/41.99          1/18.32         | 
|POLY-3 PERCENT (g) |        4.6%             0.0%             2.4%             2.4%             0.0%             5.5%            | 
|TERMINAL (d)       |        1/33 (3%)        0/22 (0%)        0/28 (0%)        0/22 (0%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        468              ---              647              307              ---              475             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.542          P=0.284N         P=0.519N         P=0.556N         P=0.254N         P=0.681         | 
|POLY 3             |        P=0.597N         P=0.257N         P=0.514N         P=0.519N         P=0.245N         P=0.664         | 
|POLY 1.5           |        P=0.627          P=0.248N         P=0.507N         P=0.515N         P=0.241N         P=0.647N        | 
|POLY 6             |        P=0.523N         P=0.272N         P=0.525N         P=0.530N         P=0.254N         P=0.501         | 
|LOGISTIC REGRESSION|        P=0.245N         P=0.211N         P=0.508N         P=0.348N         P=0.258N         P=0.295N        | 
|COCH-ARM / FISHERS |        P=0.619N         P=0.247N         P=0.500N         P=0.508N         P=0.247N         P=0.500N        | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose                                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        3/50 (6%)        0/50 (0%)        0/50 (0%)        2/49 (4%)        0/50 (0%)        1/50 (2%)       | 
|POLY-3 RATE (b)    |        3/43.61          0/39.94          0/41.60          2/41.28          0/41.99          1/18.23         | 
|POLY-3 PERCENT (g) |        6.9%             0.0%             0.0%             4.9%             0.0%             5.5%            | 
|TERMINAL (d)       |        2/33 (6%)        0/22 (0%)        0/28 (0%)        1/22 (5%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        468              ---              ---              307              ---              522             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.540          P=0.173N         P=0.143N         P=0.616N         P=0.138N         P=0.648         | 
|POLY 3             |        P=0.533N         P=0.135N         P=0.127N         P=0.525N         P=0.125N         P=0.620N        | 
|POLY 1.5           |        P=0.558N         P=0.127N         P=0.123N         P=0.519N         P=0.122N         P=0.477N        | 
|POLY 6             |        P=0.466N         P=0.148N         P=0.134N         P=0.539N         P=0.132N         P=0.557         | 
|LOGISTIC REGRESSION|        P=0.258N         P=0.110N         P=0.119N         P=0.434N         P=0.123N         P=0.335N        | 
|COCH-ARM / FISHERS |        P=0.527N         P=0.121N         P=0.121N         P=0.510N         P=0.121N         P=0.309N        | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 31      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose: Respiratory Epithelium                                                                                                     | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/50 (2%)        0/50 (0%)        1/50 (2%)        0/49 (0%)        0/50 (0%)        3/50 (6%)       | 
|POLY-3 RATE (b)    |        1/42.87          0/39.94          1/41.91          0/40.35          0/41.99          3/19.52         | 
|POLY-3 PERCENT (g) |        2.3%             0.0%             2.4%             0.0%             0.0%             15.4%           | 
|TERMINAL (d)       |        1/33 (3%)        0/22 (0%)        0/28 (0%)        0/22 (0%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        729 (T)          ---              647              ---              ---              475             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.581N         P=0.742          P=0.581N         P=0.526N         P=0.032 *       | 
|POLY 3             |        P=0.026 *        P=0.514N         P=0.756          P=0.512N         P=0.504N         P=0.110         | 
|POLY 1.5           |        P=0.022 *        P=0.507N         P=0.759          P=0.510N         P=0.501N         P=0.180         | 
|POLY 6             |        P=0.108          P=0.526N         P=0.750          P=0.518N         P=0.511N         P=0.059         | 
|LOGISTIC REGRESSION|        P=0.123          (e)              P=0.761          (e)              (e)              P=0.381         | 
|COCH-ARM / FISHERS |        P=0.031 *        P=0.500N         P=0.753N         P=0.505N         P=0.500N         P=0.309         | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        11/50 (22%)      7/49 (14%)       8/50 (16%)       9/50 (18%)       6/50 (12%)       9/50 (18%)      | 
|POLY-3 RATE (b)    |        11/44.55         7/40.72          8/44.26          9/42.25          6/42.94          9/23.66         | 
|POLY-3 PERCENT (g) |        24.7%            17.2%            18.1%            21.3%            14.0%            38.0%           | 
|TERMINAL (d)       |        8/33 (24%)       3/21 (14%)       2/28 (7%)        4/22 (18%)       4/29 (14%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        498              328              518              293              587              440             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.469N         P=0.393N         P=0.520          P=0.201N         P=0.002 **      | 
|POLY 3             |        P=0.179          P=0.280N         P=0.308N         P=0.452N         P=0.158N         P=0.206         | 
|POLY 1.5           |        P=0.299          P=0.254N         P=0.304N         P=0.432N         P=0.149N         P=0.454         | 
|POLY 6             |        P=0.131          P=0.328N         P=0.318N         P=0.489N         P=0.177N         P=0.047 *       | 
|LOGISTIC REGRESSION|        P=0.285N         P=0.214N         P=0.295N         P=0.400N         P=0.143N         P=0.449N        | 
|COCH-ARM / FISHERS |        P=0.541N         P=0.232N         P=0.306N         P=0.402N         P=0.143N         P=0.402N        | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 32      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas                                                                                                                         | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        10/50 (20%)      3/50 (6%)        9/50 (18%)       8/46 (17%)       4/50 (8%)        4/50 (8%)       | 
|POLY-3 RATE (b)    |        10/45.06         3/40.30          9/43.27          8/40.12          4/41.99          4/20.41         | 
|POLY-3 PERCENT (g) |        22.2%            7.4%             20.8%            19.9%            9.5%             19.6%           | 
|TERMINAL (d)       |        6/33 (18%)       1/22 (5%)        5/28 (18%)       6/22 (27%)       4/29 (14%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        393              643              437              646              729 (T)          405             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.078          P=0.111N         P=0.591          P=0.550          P=0.114N         P=0.191         | 
|POLY 3             |        P=0.376N         P=0.053N         P=0.540N         P=0.505N         P=0.092N         P=0.531N        | 
|POLY 1.5           |        P=0.261N         P=0.045N*        P=0.520N         P=0.492N         P=0.083N         P=0.269N        | 
|POLY 6             |        P=0.452N         P=0.070N         P=0.572N         P=0.533N         P=0.110N         P=0.359         | 
|LOGISTIC REGRESSION|        P=0.145N         P=0.033N*        P=0.491N         P=0.475N         P=0.074N         P=0.031N*       | 
|COCH-ARM / FISHERS |        P=0.101N         P=0.036N*        P=0.500N         P=0.475N         P=0.074N         P=0.074N        | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas: Acinus                                                                                                                 | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        3/50 (6%)        1/50 (2%)        0/50 (0%)        0/46 (0%)        1/50 (2%)        0/50 (0%)       | 
|POLY-3 RATE (b)    |        3/42.87          1/39.94          0/41.60          0/39.53          1/41.99          0/17.60         | 
|POLY-3 PERCENT (g) |        7.0%             2.5%             0.0%             0.0%             2.4%             0.0%            | 
|TERMINAL (d)       |        3/33 (9%)        1/22 (5%)        0/28 (0%)        0/22 (0%)        1/29 (3%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        729 (T)          729 (T)          ---              ---              729 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.755N         P=0.458N         P=0.151N         P=0.200N         P=0.352N         P=1.000N        | 
|POLY 3             |        P=0.332N         P=0.331N         P=0.124N         P=0.133N         P=0.312N         P=0.342N        | 
|POLY 1.5           |        P=0.296N         P=0.318N         P=0.121N         P=0.133N         P=0.307N         P=0.221N        | 
|POLY 6             |        P=0.413N         P=0.352N         P=0.130N         P=0.137N         P=0.324N         P=0.514N        | 
|LOGISTIC REGRESSION|        P=0.755N         P=0.458N         (e)              (e)              P=0.352N         (e)             | 
|COCH-ARM / FISHERS |        P=0.239N         P=0.309N         P=0.121N         P=0.137N         P=0.309N         P=0.121N        | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 33      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Angiectasis                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        6/50 (12%)       6/48 (13%)       8/50 (16%)       8/49 (16%)       9/50 (18%)       7/49 (14%)      | 
|POLY-3 RATE (b)    |        6/43.61          6/39.53          8/42.78          8/41.54          9/43.64          7/21.98         | 
|POLY-3 PERCENT (g) |        13.8%            15.2%            18.7%            19.3%            20.6%            31.9%           | 
|TERMINAL (d)       |        5/33 (15%)       1/21 (5%)        6/28 (21%)       4/22 (18%)       5/29 (17%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        468              605              437              638              463              400             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.405          P=0.291          P=0.214          P=0.229          P=0.003 **      | 
|POLY 3             |        P=0.082          P=0.551          P=0.370          P=0.348          P=0.286          P=0.097         | 
|POLY 1.5           |        P=0.200          P=0.569          P=0.381          P=0.352          P=0.290          P=0.231         | 
|POLY 6             |        P=0.036 *        P=0.525          P=0.349          P=0.339          P=0.273          P=0.024 *       | 
|LOGISTIC REGRESSION|        P=0.471          P=0.586          P=0.386          P=0.358          P=0.288          P=0.665N        | 
|COCH-ARM / FISHERS |        P=0.504          P=0.591          P=0.387          P=0.371          P=0.288          P=0.484         | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        16/50 (32%)      11/48 (23%)      19/50 (38%)      16/49 (33%)      17/50 (34%)      19/49 (39%)     | 
|POLY-3 RATE (b)    |        16/43.90         11/39.85         19/45.73         16/41.52         17/45.37         19/29.81        | 
|POLY-3 PERCENT (g) |        36.4%            27.6%            41.6%            38.5%            37.5%            63.7%           | 
|TERMINAL (d)       |        14/33 (42%)      5/21 (24%)       10/28 (36%)      10/22 (46%)      8/29 (28%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        483              541              437              618              463              350             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.570N         P=0.212          P=0.181          P=0.373          P<0.001 **      | 
|POLY 3             |        P=0.010 *        P=0.262N         P=0.389          P=0.510          P=0.548          P=0.016 *       | 
|POLY 1.5           |        P=0.038 *        P=0.241N         P=0.373          P=0.521          P=0.532          P=0.080         | 
|POLY 6             |        P=0.002 **       P=0.299N         P=0.399          P=0.486          P=0.559          P<0.001 **      | 
|LOGISTIC REGRESSION|        P=0.099          P=0.283N         P=0.336          P=0.492          P=0.496          P=0.235         | 
|COCH-ARM / FISHERS |        P=0.183          P=0.218N         P=0.338          P=0.558          P=0.500          P=0.310         | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 34      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        10/50 (20%)      8/48 (17%)       9/50 (18%)       11/49 (22%)      7/50 (14%)       6/49 (12%)      | 
|POLY-3 RATE (b)    |        10/42.87         8/40.66          9/42.54          11/41.23         7/42.94          6/20.85         | 
|POLY-3 PERCENT (g) |        23.3%            19.7%            21.2%            26.7%            16.3%            28.8%           | 
|TERMINAL (d)       |        10/33 (30%)      1/21 (5%)        7/28 (25%)       8/22 (36%)       4/29 (14%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        729 (T)          513              562              638              581              469             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.512          P=0.563          P=0.176          P=0.391N         P<0.001 **      | 
|POLY 3             |        P=0.493          P=0.445N         P=0.508N         P=0.459          P=0.292N         P=0.441         | 
|POLY 1.5           |        P=0.408N         P=0.439N         P=0.501N         P=0.461          P=0.291N         P=0.515N        | 
|POLY 6             |        P=0.395          P=0.460N         P=0.526N         P=0.448          P=0.302N         P=0.166         | 
|LOGISTIC REGRESSION|        P=0.539          P=0.467N         P=0.567N         P=0.372          P=0.338N         P=0.214         | 
|COCH-ARM / FISHERS |        P=0.151N         P=0.435N         P=0.500N         P=0.479          P=0.298N         P=0.220N        | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Salivary Glands                                                                                                                  | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/50 (0%)        0/50 (0%)        0/50 (0%)        1/50 (2%)        0/50 (0%)        2/50 (4%)       | 
|POLY-3 RATE (b)    |        0/42.87          0/39.94          0/41.60          1/40.79          0/41.99          2/18.79         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             2.5%             0.0%             10.7%           | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        0/28 (0%)        1/22 (5%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              ---              729 (T)          ---              527             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.419          (e)              P=0.076         | 
|POLY 3             |        P=0.030 *        (e)              (e)              P=0.490          (e)              P=0.113         | 
|POLY 1.5           |        P=0.030 *        (e)              (e)              P=0.493          (e)              P=0.158         | 
|POLY 6             |        P=0.104          (e)              (e)              P=0.483          (e)              P=0.079         | 
|LOGISTIC REGRESSION|        P=0.093          (e)              (e)              P=0.419          (e)              P=0.357         | 
|COCH-ARM / FISHERS |        P=0.047 *        (e)              (e)              P=0.500          (e)              P=0.247         | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 35      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skeletal Muscle                                                                                                                  | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/0 (0%)         0/1 (0%)         0/1 (0%)         0/2 (0%)         0/0 (0%)         4/6 (67%)       | 
|POLY-3 RATE (b)    |        0/0.00           0/0.88           0/0.53           0/0.68           0/0.00           4/4.68          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             85.5%           | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              476             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              (e)              (e)              P=0.005 **      | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        P=0.057          (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.051          (e)              (e)              (e)              (e)              P=1.000         | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin: Subcutaneous Tissue                                                                                                        | 
|     Edema                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/50 (0%)        0/50 (0%)        0/49 (0%)        2/50 (4%)        0/50 (0%)        0/50 (0%)       | 
|POLY-3 RATE (b)    |        0/42.87          0/39.94          0/40.60          2/41.23          0/41.99          0/17.60         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             4.9%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        0/27 (0%)        0/22 (0%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              ---              618              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.949N         (e)              (e)              P=0.211          (e)              (e)             | 
|POLY 3             |        P=0.591N         (e)              (e)              P=0.228          (e)              (e)             | 
|POLY 1.5           |        P=0.563N         (e)              (e)              P=0.231          (e)              (e)             | 
|POLY 6             |        P=0.724N         (e)              (e)              P=0.223          (e)              (e)             | 
|LOGISTIC REGRESSION|        P=0.629N         (e)              (e)              P=0.239          (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.534N         (e)              (e)              P=0.247          (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 36      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Congestion                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/50 (0%)        0/50 (0%)        0/50 (0%)        1/50 (2%)        3/50 (6%)        7/50 (14%)      | 
|POLY-3 RATE (b)    |        0/42.87          0/39.94          0/41.60          1/41.09          3/42.47          7/22.30         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             2.4%             7.1%             31.4%           | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        0/28 (0%)        0/22 (0%)        2/29 (7%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              ---              646              587              393             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.505          P=0.108          P<0.001 **      | 
|POLY 3             |        P<0.001 **       (e)              (e)              P=0.492          P=0.116          P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P=0.494          P=0.119          P<0.001 **      | 
|POLY 6             |        P<0.001 **       (e)              (e)              P=0.486          P=0.112          P<0.001 **      | 
|LOGISTIC REGRESSION|        P=0.003 **       (e)              (e)              P=0.511          P=0.120          P=0.109         | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P=0.500          P=0.121          P=0.006 **      | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Fibrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/50 (2%)        1/50 (2%)        2/50 (4%)        0/50 (0%)        2/50 (4%)        0/50 (0%)       | 
|POLY-3 RATE (b)    |        1/42.87          1/40.16          2/41.60          0/40.79          2/42.47          0/17.60         | 
|POLY-3 PERCENT (g) |        2.3%             2.5%             4.8%             0.0%             4.7%             0.0%            | 
|TERMINAL (d)       |        1/33 (3%)        0/22 (0%)        2/28 (7%)        0/22 (0%)        1/29 (3%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        729 (T)          672              729 (T)          ---              587              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.721          P=0.692          P=0.442          P=0.581N         P=0.470          P=1.000N        | 
|POLY 3             |        P=0.581N         P=0.746          P=0.490          P=0.510N         P=0.497          P=0.650N        | 
|POLY 1.5           |        P=0.457N         P=0.753          P=0.496          P=0.507N         P=0.500          P=0.586N        | 
|POLY 6             |        P=0.488          P=0.734          P=0.478          P=0.517N         P=0.488          P=0.716N        | 
|LOGISTIC REGRESSION|        P=0.647N         P=0.747          P=0.442          (e)              P=0.500          (e)             | 
|COCH-ARM / FISHERS |        P=0.321N         P=0.753N         P=0.500          P=0.500N         P=0.500          P=0.500N        | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 37      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        24/50 (48%)      33/50 (66%)      25/50 (50%)      26/50 (52%)      27/50 (54%)      34/50 (68%)     | 
|POLY-3 RATE (b)    |        24/46.90         33/46.20         25/46.39         26/44.48         27/44.37         34/38.85        | 
|POLY-3 PERCENT (g) |        51.2%            71.4%            53.9%            58.5%            60.9%            87.5%           | 
|TERMINAL (d)       |        16/33 (49%)      15/22 (68%)      14/28 (50%)      12/22 (55%)      19/29 (66%)      0/0 (0%)        | 
|FIRST INCIDENCE    |        393              328              437              307              524              350             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.006 **       P=0.322          P=0.100          P=0.203          P<0.001 **      | 
|POLY 3             |        P<0.001 **       P=0.031 *        P=0.478          P=0.310          P=0.230          P<0.001 **      | 
|POLY 1.5           |        P=0.005 **       P=0.038 *        P=0.486          P=0.341          P=0.277          P<0.001 **      | 
|POLY 6             |        P<0.001 **       P=0.024 *        P=0.469          P=0.280          P=0.175          P<0.001 **      | 
|LOGISTIC REGRESSION|        P=0.024 *        P=0.058          P=0.515          P=0.408          P=0.339          P=0.088         | 
|COCH-ARM / FISHERS |        P=0.057          P=0.053          P=0.500          P=0.421          P=0.345          P=0.034 *       | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        37/50 (74%)      41/50 (82%)      35/50 (70%)      34/50 (68%)      35/50 (70%)      29/50 (58%)     | 
|POLY-3 RATE (b)    |        37/46.55         41/46.41         35/46.77         34/46.15         35/45.40         29/36.54        | 
|POLY-3 PERCENT (g) |        79.5%            88.3%            74.8%            73.7%            77.1%            79.4%           | 
|TERMINAL (d)       |        27/33 (82%)      21/22 (96%)      20/28 (71%)      16/22 (73%)      25/29 (86%)      0/0 (0%)        | 
|FIRST INCIDENCE    |        468              328              444              252              524              393             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.007 **       P=0.396          P=0.168          P=0.444          P<0.001 **      | 
|POLY 3             |        P=0.484N         P=0.171          P=0.382N         P=0.332N         P=0.489N         P=0.615N        | 
|POLY 1.5           |        P=0.173N         P=0.203          P=0.381N         P=0.325N         P=0.438N         P=0.279N        | 
|POLY 6             |        P=0.239          P=0.122          P=0.409N         P=0.370N         P=0.598N         P=0.215         | 
|LOGISTIC REGRESSION|        P=0.547          P=0.154          P=0.431N         P=0.389N         P=0.417N         P=0.615N        | 
|COCH-ARM / FISHERS |        P=0.017N*        P=0.235          P=0.412N         P=0.330N         P=0.412N         P=0.069N        | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 38      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Ulcer                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/50 (0%)        0/50 (0%)        2/50 (4%)        0/49 (0%)        0/49 (0%)        0/50 (0%)       | 
|POLY-3 RATE (b)    |        0/42.87          0/39.94          2/41.66          0/40.71          0/40.99          0/17.60         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             4.8%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        1/28 (4%)        0/22 (0%)        0/28 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              715              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.887N         (e)              P=0.209          (e)              (e)              (e)             | 
|POLY 3             |        P=0.396N         (e)              P=0.230          (e)              (e)              (e)             | 
|POLY 1.5           |        P=0.414N         (e)              P=0.234          (e)              (e)              (e)             | 
|POLY 6             |        P=0.458N         (e)              P=0.223          (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        P=0.854N         (e)              P=0.213          (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.429N         (e)              P=0.247          (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach: Epithelium                                                                                                 | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/50 (0%)        1/50 (2%)        5/50 (10%)       1/49 (2%)        1/49 (2%)        3/50 (6%)       | 
|POLY-3 RATE (b)    |        0/42.87          1/40.38          5/43.05          1/40.91          1/41.42          3/19.34         | 
|POLY-3 PERCENT (g) |        0.0%             2.5%             11.6%            2.4%             2.4%             15.5%           | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        1/28 (4%)        0/22 (0%)        0/28 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              600              437              678              602              488             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.003 **       P=0.495          P=0.030 *        P=0.477          P=0.491          P=0.009 **      | 
|POLY 3             |        P=0.162          P=0.488          P=0.030 *        P=0.491          P=0.493          P=0.037 *       | 
|POLY 1.5           |        P=0.197          P=0.494          P=0.031 *        P=0.493          P=0.495          P=0.062         | 
|POLY 6             |        P=0.239          P=0.478          P=0.029 *        P=0.485          P=0.488          P=0.022 *       | 
|LOGISTIC REGRESSION|        P=0.587          P=0.522          P=0.032 *        P=0.496          P=0.476          P=0.184         | 
|COCH-ARM / FISHERS |        P=0.313          P=0.500          P=0.028 *        P=0.495          P=0.495          P=0.121         | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 39      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular                                                                                                               | 
|     Erosion                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/50 (0%)        0/50 (0%)        0/50 (0%)        2/49 (4%)        1/49 (2%)        9/50 (18%)      | 
|POLY-3 RATE (b)    |        0/42.87          0/39.94          0/41.60          2/41.81          1/41.42          9/23.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             4.8%             2.4%             39.1%           | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        0/28 (0%)        0/22 (0%)        0/28 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              ---              451              602              405             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.245          P=0.491          P<0.001 **      | 
|POLY 3             |        P<0.001 **       (e)              (e)              P=0.231          P=0.493          P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P=0.232          P=0.495          P<0.001 **      | 
|POLY 6             |        P<0.001 **       (e)              (e)              P=0.227          P=0.488          P<0.001 **      | 
|LOGISTIC REGRESSION|        P<0.001 **       (e)              (e)              P=0.278          P=0.476          P=0.014 *       | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P=0.242          P=0.495          P<0.001 **      | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular                                                                                                               | 
|     Ulcer                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/50 (0%)        0/50 (0%)        0/50 (0%)        2/49 (4%)        0/49 (0%)        7/50 (14%)      | 
|POLY-3 RATE (b)    |        0/42.87          0/39.94          0/41.60          2/42.19          0/40.99          7/21.66         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             4.7%             0.0%             32.3%           | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        0/28 (0%)        0/22 (0%)        0/28 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              ---              307              ---              405             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.238          (e)              P<0.001 **      | 
|POLY 3             |        P<0.001 **       (e)              (e)              P=0.233          (e)              P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P=0.234          (e)              P<0.001 **      | 
|POLY 6             |        P<0.001 **       (e)              (e)              P=0.228          (e)              P<0.001 **      | 
|LOGISTIC REGRESSION|        P=0.012 *        (e)              (e)              P=0.347          (e)              P=0.021 *       | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P=0.242          (e)              P=0.006 **      | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 40      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/48 (0%)        2/48 (4%)        0/46 (0%)        0/48 (0%)        0/50 (0%)        2/49 (4%)       | 
|POLY-3 RATE (b)    |        0/41.55          2/39.43          0/37.91          0/39.12          0/41.99          2/18.39         | 
|POLY-3 PERCENT (g) |        0.0%             5.1%             0.0%             0.0%             0.0%             10.9%           | 
|TERMINAL (d)       |        0/32 (0%)        0/21 (0%)        0/25 (0%)        0/22 (0%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              519              ---              ---              ---              393             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.028 *        P=0.242          (e)              (e)              (e)              P=0.096         | 
|POLY 3             |        P=0.141          P=0.225          (e)              (e)              (e)              P=0.115         | 
|POLY 1.5           |        P=0.130          P=0.231          (e)              (e)              (e)              P=0.160         | 
|POLY 6             |        P=0.336          P=0.216          (e)              (e)              (e)              P=0.079         | 
|LOGISTIC REGRESSION|        P=0.514          P=0.278          (e)              (e)              (e)              P=0.581         | 
|COCH-ARM / FISHERS |        P=0.167          P=0.247          (e)              (e)              (e)              P=0.253         | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland                                                                                                                    | 
|     Ultimobranchial Cyst                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/49 (2%)        2/50 (4%)        0/49 (0%)        0/49 (0%)        1/50 (2%)        2/50 (4%)       | 
|POLY-3 RATE (b)    |        1/42.28          2/40.37          0/41.38          0/40.72          1/42.75          2/18.68         | 
|POLY-3 PERCENT (g) |        2.4%             5.0%             0.0%             0.0%             2.3%             10.7%           | 
|TERMINAL (d)       |        0/32 (0%)        1/22 (5%)        0/28 (0%)        0/22 (0%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        611              605              ---              ---              451              552             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.013 *        P=0.444          P=0.514N         P=0.500N         P=0.757          P=0.053         | 
|POLY 3             |        P=0.153          P=0.484          P=0.504N         P=0.508N         P=0.758N         P=0.261         | 
|POLY 1.5           |        P=0.178          P=0.495          P=0.501N         P=0.504N         P=0.756N         P=0.363         | 
|POLY 6             |        P=0.248          P=0.464          P=0.511N         P=0.515N         P=0.757          P=0.168         | 
|LOGISTIC REGRESSION|        P=0.558          P=0.522          P=0.524N         P=0.482N         P=0.698          P=0.595         | 
|COCH-ARM / FISHERS |        P=0.270          P=0.508          P=0.500N         P=0.500N         P=0.747N         P=0.508         | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 41      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: C-Cell                                                                                                            | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        22/49 (45%)      9/50 (18%)       24/49 (49%)      15/49 (31%)      20/50 (40%)      10/50 (20%)     | 
|POLY-3 RATE (b)    |        22/43.58         9/40.81          24/42.74         15/42.19         20/43.90         10/23.16        | 
|POLY-3 PERCENT (g) |        50.5%            22.1%            56.2%            35.6%            45.6%            43.2%           | 
|TERMINAL (d)       |        19/32 (59%)      6/22 (27%)       19/28 (68%)      8/22 (36%)       15/29 (52%)      0/0 (0%)        | 
|FIRST INCIDENCE    |        393              573              518              561              463              352             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.056N         P=0.211          P=0.475N         P=0.570N         P<0.001 **      | 
|POLY 3             |        P=0.449          P=0.004N**       P=0.373          P=0.113N         P=0.400N         P=0.381N        | 
|POLY 1.5           |        P=0.281N         P=0.004N**       P=0.398          P=0.113N         P=0.391N         P=0.090N        | 
|POLY 6             |        P=0.181          P=0.006N**       P=0.330          P=0.116N         P=0.422N         P=0.313         | 
|LOGISTIC REGRESSION|        P=0.138          P=0.006N**       P=0.390          P=0.117N         P=0.402N         P=0.625N        | 
|COCH-ARM / FISHERS |        P=0.031N*        P=0.004N**       P=0.420          P=0.105N         P=0.386N         P=0.007N**      | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Hydrometra                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/50 (10%)       7/50 (14%)       0/50 (0%)        6/50 (12%)       6/50 (12%)       6/50 (12%)      | 
|POLY-3 RATE (b)    |        5/43.24          7/41.97          0/41.60          6/41.89          6/42.56          6/21.54         | 
|POLY-3 PERCENT (g) |        11.6%            16.7%            0.0%             14.3%            14.1%            27.9%           | 
|TERMINAL (d)       |        4/33 (12%)       0/22 (0%)        0/28 (0%)        3/22 (14%)       3/29 (10%)       0/0 (0%)        | 
|FIRST INCIDENCE    |        626              541              ---              451              654              407             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.245          P=0.048N*        P=0.313          P=0.424          P=0.002 **      | 
|POLY 3             |        P=0.048 *        P=0.357          P=0.033N*        P=0.478          P=0.489          P=0.119         | 
|POLY 1.5           |        P=0.111          P=0.368          P=0.032N*        P=0.485          P=0.497          P=0.258         | 
|POLY 6             |        P=0.029 *        P=0.339          P=0.037N*        P=0.459          P=0.470          P=0.035 *       | 
|LOGISTIC REGRESSION|        P=0.320          P=0.382          P=0.037N*        P=0.486          P=0.478          P=0.519         | 
|COCH-ARM / FISHERS |        P=0.304          P=0.380          P=0.028N*        P=0.500          P=0.500          P=0.500         | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  12/15/00                           EXPERIMENT: 05161 TEST: 05                                            Page 42      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                    RIDDELLIINE    
                                         Terminal Sacrifice at 105 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/50 (8%)        3/50 (6%)        7/50 (14%)       5/50 (10%)       2/50 (4%)        9/50 (18%)      | 
|POLY-3 RATE (b)    |        4/42.87          3/39.99          7/42.39          5/41.10          2/42.34          9/23.06         | 
|POLY-3 PERCENT (g) |        9.3%             7.5%             16.5%            12.2%            4.7%             39.0%           | 
|TERMINAL (d)       |        4/33 (12%)       2/22 (9%)        6/28 (21%)       3/22 (14%)       1/29 (3%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        729 (T)          718              437              660              630              472             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.603          P=0.180          P=0.288          P=0.390N         P<0.001 **      | 
|POLY 3             |        P=0.017 *        P=0.538N         P=0.252          P=0.473          P=0.342N         P=0.007 **      | 
|POLY 1.5           |        P=0.027 *        P=0.520N         P=0.260          P=0.482          P=0.338N         P=0.028 *       | 
|POLY 6             |        P=0.021 *        P=0.570N         P=0.236          P=0.456          P=0.354N         P<0.001 **      | 
|LOGISTIC REGRESSION|        P=0.017 *        P=0.648          P=0.242          P=0.405          P=0.360N         P=0.043 *       | 
|COCH-ARM / FISHERS |        P=0.070          P=0.500N         P=0.262          P=0.500          P=0.339N         P=0.117         | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0                0.01             0.033            0.1              0.33             1.0             | 
|                   |        MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY         MG/KG/DY        | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/50 (0%)        0/50 (0%)        2/50 (4%)        0/50 (0%)        1/50 (2%)        0/50 (0%)       | 
|POLY-3 RATE (b)    |        0/42.87          0/39.94          2/41.60          0/40.79          1/42.25          0/17.60         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             4.8%             0.0%             2.4%             0.0%            | 
|TERMINAL (d)       |        0/33 (0%)        0/22 (0%)        2/28 (7%)        0/22 (0%)        0/29 (0%)        0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              729 (T)          ---              658              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.842          (e)              P=0.202          (e)              P=0.484          (e)             | 
|POLY 3             |        P=0.620          (e)              P=0.230          (e)              P=0.497          (e)             | 
|POLY 1.5           |        P=0.578N         (e)              P=0.234          (e)              P=0.499          (e)             | 
|POLY 6             |        P=0.544          (e)              P=0.223          (e)              P=0.492          (e)             | 
|LOGISTIC REGRESSION|        P=0.846          (e)              P=0.202          (e)              P=0.498          (e)             | 
|COCH-ARM / FISHERS |        P=0.496N         (e)              P=0.247          (e)              P=0.500          (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).                                                    

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