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TDMS Study 99035-01 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                          TRANSGENIC MODEL EVALUATION II (GLYCIDOL)                      DATE: 04/14/04       
EXPERIMENT: 99035 TEST: 01                                                                                     TIME: 10:53:58       
TEST TYPE:  26-39 WEEKS                         CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-65406                              ROUTE: GAVAGE                                                  NTP C#: C99035       
PATHOLOGIST: MISSING                                                                                           CAS: 556-52-5        
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                           FINAL #1 MICE                                                            
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
                                                                                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                          TRANSGENIC MODEL EVALUATION II (GLYCIDOL)                      DATE: 04/14/04       
EXPERIMENT: 99035 TEST: 01                                                                                     TIME: 10:53:58       
TEST TYPE:  26-39 WEEKS                         CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-65406                              ROUTE: GAVAGE                                                  NTP C#: C99035       
PATHOLOGIST: MISSING                                                                                           CAS: 556-52-5        
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF        TRANSGENIC MODEL EVALUATION II (GLY                                                                       
===============================================================                                                                     
Male Mice                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Brain: Cerebellum                      Gliosis                                                                                      
                                       Neuronopathy                                                                                 
Brain: Cerebrum                        Necrosis Focal                                                                               
Brain: Medulla                         Gliosis                                                                                      
                                       Neuronopathy                                                                                 
Brain: Thalamus                        Gliosis                                                                                      
                                       Neuronopathy                                                                                 
Heart: Myocardium                      Degeneration                                                                                 
                                       Mineralization                                                                               
                                       Necrosis                                                                                     
Liver                                  Inflammation Chronic                                                                         
                                       Necrosis Focal                                                                               
Spleen                                 Atrophy                                                                                      
Stomach, Forestomach                   Ulcer                                                                                        
Stomach, Forestomach: Epithelium       Hyperplasia                                                                                  
Stomach, Glandular                     Mineralization                                                                               
Thymus                                 Atrophy                                                                                      
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Adrenal Cortex: Subcapsular            Hyperplasia                                                                                  
Brain: Cerebellum                      Neuronopathy                                                                                 
Brain: Medulla                         Gliosis                                                                                      
                                       Neuronopathy                                                                                 
Brain: Thalamus                        Neuronopathy                                                                                 
Kidney: Renal Tubule                   Accumulation, Hyaline Droplet                                                                
Liver                                  Angiectasis Focal                                                                            
                                       Necrosis Focal                                                                               
Lung                                   Inflammation                                                                                 
Lymph Node: Mediastinal                Hyperplasia Lymphoid                                                                         
Ovary                                  Cyst                                                                                         
Spleen                                 Hematopoietic Cell Proliferation                                                             
Stomach, Forestomach: Epithelium       Hyperplasia                                                                                  
Stomach, Glandular                     Mineralization                                                                               
Stomach, Glandular: Muscularis         Mineralization                                                                               
Thymus                                 Atrophy                                                                                      
===============================================================                                                                     
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions in        Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II 
(GLY                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        0/15 (0%)        0/15 (0%)        1/14 (7%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        1/13.95          0/14.74          0/13.80          1/14.00          0/11.42                          | 
|POLY-3 PERCENT (g) |        7.2%             0.0%             0.0%             7.1%             0.0%                             | 
|TERMINAL (d)       |        1/13 (8%)        0/14 (0%)        0/13 (0%)        1/14 (7%)        0/7 (0%)                         | 
|FIRST INCIDENCE    |        280 (T)          ---              ---              280 (T)          ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.617N         P=0.485N         P=0.500N         P=0.748N         P=0.623N                         | 
|POLY 3             |        P=0.533N         P=0.489N         P=0.502N         P=0.760N         P=0.540N                         | 
|POLY 1.5           |        P=0.522N         P=0.493N         P=0.502N         P=0.755          P=0.522N                         | 
|POLY 6             |        P=0.545N         P=0.485N         P=0.500N         P=0.752N         P=0.562N                         | 
|LOGISTIC REGRESSION|        P=0.617N         (e)              (e)              P=0.748N         (e)                              | 
|COCH-ARM / FISHERS |        P=0.503N         P=0.500N         P=0.500N         P=0.741          P=0.500N                         | 
|ORDER RESTRICTED   |        P=0.271N         (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        2/15 (13%)       0/15 (0%)        0/15 (0%)        1/15 (7%)                        | 
|POLY-3 RATE (b)    |        0/13.88          2/14.62          0/14.15          0/14.62          1/12.41                          | 
|POLY-3 PERCENT (g) |        0.0%             13.7%            0.0%             0.0%             8.1%                             | 
|TERMINAL (d)       |        0/13 (0%)        2/14 (14%)       0/12 (0%)        0/14 (0%)        1/9 (11%)                        | 
|FIRST INCIDENCE    |        ---              281 (T)          ---              ---              281 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.503          P=0.252          (e)              (e)              P=0.427                          | 
|POLY 3             |        P=0.566          P=0.243          (e)              (e)              P=0.478                          | 
|POLY 1.5           |        P=0.576          P=0.243          (e)              (e)              P=0.488                          | 
|POLY 6             |        P=0.556          P=0.242          (e)              (e)              P=0.466                          | 
|LOGISTIC REGRESSION|        (e)              P=0.252          (e)              (e)              P=0.427                          | 
|COCH-ARM / FISHERS |        P=0.583          P=0.241          (e)              (e)              P=0.500                          | 
|ORDER RESTRICTED   |        P=0.277          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 2       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex: Subcapsular                                                                                                      | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        2/15 (13%)       2/15 (13%)       3/14 (21%)       1/15 (7%)                        | 
|POLY-3 RATE (b)    |        1/13.95          2/14.74          2/13.80          3/14.00          1/11.42                          | 
|POLY-3 PERCENT (g) |        7.2%             13.6%            14.5%            21.4%            8.8%                             | 
|TERMINAL (d)       |        1/13 (8%)        2/14 (14%)       2/13 (15%)       3/14 (21%)       1/7 (14%)                        | 
|FIRST INCIDENCE    |        280 (T)          280 (T)          280 (T)          280 (T)          280 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.408          P=0.527          P=0.500          P=0.325          P=0.620                          | 
|POLY 3             |        P=0.499          P=0.519          P=0.496          P=0.298          P=0.715                          | 
|POLY 1.5           |        P=0.560          P=0.512          P=0.496          P=0.288          P=0.736                          | 
|POLY 6             |        P=0.423          P=0.527          P=0.499          P=0.311          P=0.686                          | 
|LOGISTIC REGRESSION|        P=0.408          P=0.527          P=0.500          P=0.325          P=0.620                          | 
|COCH-ARM / FISHERS |        P=0.556N         P=0.500          P=0.500          P=0.272          P=0.759N                         | 
|ORDER RESTRICTED   |        P=0.480          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex: Subcapsular                                                                                                      | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        15/15 (100%)     15/15 (100%)     10/15 (67%)      14/15 (93%)      15/15 (100%)                     | 
|POLY-3 RATE (b)    |        15/15.00         15/15.00         10/14.59         14/15.00         15/15.00                         | 
|POLY-3 PERCENT (g) |        100.0%           100.0%           68.6%            93.3%            100.0%                           | 
|TERMINAL (d)       |        13/13 (100%)     14/14 (100%)     9/12 (75%)       13/14 (93%)      9/9 (100%)                       | 
|FIRST INCIDENCE    |        83               239              232              239              133                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.017 *        (e)              P=0.097N         P=0.309N         (e)                              | 
|POLY 3             |        P=0.396          (e)              P=0.020N*        P=0.500N         (e)                              | 
|POLY 1.5           |        P=0.384          (e)              P=0.018N*        P=0.500N         (e)                              | 
|POLY 6             |        P=0.414          (e)              P=0.025N*        P=0.500N         (e)                              | 
|LOGISTIC REGRESSION|        P=0.392          (e)              P=0.025N*        (e)              (e)                              | 
|COCH-ARM / FISHERS |        P=0.382          (e)              P=0.021N*        P=0.500N         (e)                              | 
|ORDER RESTRICTED   |        P=0.115N         (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 3       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain: Cerebellum                                                                                                                | 
|     Gliosis                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        2/15 (13%)                       | 
|POLY-3 RATE (b)    |        0/13.95          0/14.74          0/13.80          0/14.37          2/12.20                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             16.4%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/13 (0%)        0/14 (0%)        0/7 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              210                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.013 *        (e)              (e)              (e)              P=0.192                          | 
|POLY 3             |        P=0.016 *        (e)              (e)              (e)              P=0.200                          | 
|POLY 1.5           |        P=0.017 *        (e)              (e)              (e)              P=0.213                          | 
|POLY 6             |        P=0.016 *        (e)              (e)              (e)              P=0.185                          | 
|LOGISTIC REGRESSION|        P=0.053          (e)              (e)              (e)              P=0.345                          | 
|COCH-ARM / FISHERS |        P=0.021 *        (e)              (e)              (e)              P=0.241                          | 
|ORDER RESTRICTED   |        P=0.009 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain: Cerebellum                                                                                                                | 
|     Gliosis                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        1/15 (7%)                        | 
|POLY-3 RATE (b)    |        0/13.88          0/14.62          0/14.15          0/14.62          1/13.01                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             7.7%                             | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/12 (0%)        0/14 (0%)        0/9 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              208                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.129          (e)              (e)              (e)              P=0.485                          | 
|POLY 3             |        P=0.135          (e)              (e)              (e)              P=0.487                          | 
|POLY 1.5           |        P=0.138          (e)              (e)              (e)              P=0.494                          | 
|POLY 6             |        P=0.132          (e)              (e)              (e)              P=0.480                          | 
|LOGISTIC REGRESSION|        P=0.177          (e)              (e)              (e)              P=0.498                          | 
|COCH-ARM / FISHERS |        P=0.143          (e)              (e)              (e)              P=0.500                          | 
|ORDER RESTRICTED   |        P=0.077          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 4       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain: Cerebellum                                                                                                                | 
|     Neuronopathy                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        3/15 (20%)                       | 
|POLY-3 RATE (b)    |        0/13.95          0/14.74          0/13.80          0/14.37          3/12.93                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             23.2%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/13 (0%)        0/14 (0%)        0/7 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              181                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.002 **       (e)              (e)              (e)              P=0.099                          | 
|POLY 3             |        P=0.002 **       (e)              (e)              (e)              P=0.090                          | 
|POLY 1.5           |        P=0.002 **       (e)              (e)              (e)              P=0.097                          | 
|POLY 6             |        P=0.002 **       (e)              (e)              (e)              P=0.082                          | 
|LOGISTIC REGRESSION|        P=0.019 *        (e)              (e)              (e)              P=0.277                          | 
|COCH-ARM / FISHERS |        P=0.003 **       (e)              (e)              (e)              P=0.112                          | 
|ORDER RESTRICTED   |        P=0.002 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain: Cerebellum                                                                                                                | 
|     Neuronopathy                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        1/15 (7%)        3/15 (20%)                       | 
|POLY-3 RATE (b)    |        0/13.88          0/14.62          0/14.15          1/14.62          3/13.90                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             6.8%             21.6%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/12 (0%)        1/14 (7%)        1/9 (11%)                        | 
|FIRST INCIDENCE    |        ---              ---              ---              281 (T)          133                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.003 **       (e)              (e)              P=0.515          P=0.102                          | 
|POLY 3             |        P=0.004 **       (e)              (e)              P=0.510          P=0.105                          | 
|POLY 1.5           |        P=0.004 **       (e)              (e)              P=0.510          P=0.108                          | 
|POLY 6             |        P=0.004 **       (e)              (e)              P=0.509          P=0.100                          | 
|LOGISTIC REGRESSION|        P=0.012 *        (e)              (e)              P=0.515          P=0.104                          | 
|COCH-ARM / FISHERS |        P=0.005 **       (e)              (e)              P=0.500          P=0.112                          | 
|ORDER RESTRICTED   |        P=0.008 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 5       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain: Cerebrum                                                                                                                  | 
|     Necrosis Focal                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        2/15 (13%)                       | 
|POLY-3 RATE (b)    |        0/13.95          0/14.74          0/13.80          0/14.37          2/12.04                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             16.6%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/13 (0%)        0/14 (0%)        0/7 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              210                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.011 *        (e)              (e)              (e)              P=0.180                          | 
|POLY 3             |        P=0.016 *        (e)              (e)              (e)              P=0.197                          | 
|POLY 1.5           |        P=0.017 *        (e)              (e)              (e)              P=0.211                          | 
|POLY 6             |        P=0.016 *        (e)              (e)              (e)              P=0.180                          | 
|LOGISTIC REGRESSION|        P=0.046 *        (e)              (e)              (e)              P=0.306                          | 
|COCH-ARM / FISHERS |        P=0.021 *        (e)              (e)              (e)              P=0.241                          | 
|ORDER RESTRICTED   |        P=0.009 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain: Cerebrum                                                                                                                  | 
|     Necrosis Focal                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        0/13.88          0/14.62          0/14.15          0/14.62          0/12.41                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%                             | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/12 (0%)        0/14 (0%)        0/9 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)                              | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)                              | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)                              | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)                              | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)                              | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)                              | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 6       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain: Medulla                                                                                                                   | 
|     Gliosis                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        2/15 (13%)                       | 
|POLY-3 RATE (b)    |        0/13.95          0/14.74          0/13.80          0/14.37          2/12.73                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             15.7%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/13 (0%)        0/14 (0%)        0/7 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              181                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.021 *        (e)              (e)              (e)              P=0.232                          | 
|POLY 3             |        P=0.017 *        (e)              (e)              (e)              P=0.209                          | 
|POLY 1.5           |        P=0.018 *        (e)              (e)              (e)              P=0.219                          | 
|POLY 6             |        P=0.016 *        (e)              (e)              (e)              P=0.195                          | 
|LOGISTIC REGRESSION|        P=0.062          (e)              (e)              (e)              P=0.476                          | 
|COCH-ARM / FISHERS |        P=0.021 *        (e)              (e)              (e)              P=0.241                          | 
|ORDER RESTRICTED   |        P=0.010 *        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain: Medulla                                                                                                                   | 
|     Gliosis                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        2/15 (13%)                       | 
|POLY-3 RATE (b)    |        0/13.88          0/14.62          0/14.15          0/14.62          2/13.31                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             15.0%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/12 (0%)        0/14 (0%)        1/9 (11%)                        | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              133                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.015 *        (e)              (e)              (e)              P=0.207                          | 
|POLY 3             |        P=0.018 *        (e)              (e)              (e)              P=0.221                          | 
|POLY 1.5           |        P=0.018 *        (e)              (e)              (e)              P=0.229                          | 
|POLY 6             |        P=0.017 *        (e)              (e)              (e)              P=0.210                          | 
|LOGISTIC REGRESSION|        P=0.037 *        (e)              (e)              (e)              P=0.225                          | 
|COCH-ARM / FISHERS |        P=0.021 *        (e)              (e)              (e)              P=0.241                          | 
|ORDER RESTRICTED   |        P=0.012 *        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 7       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain: Medulla                                                                                                                   | 
|     Neuronopathy                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        3/15 (20%)                       | 
|POLY-3 RATE (b)    |        0/13.95          0/14.74          0/13.80          0/14.37          3/12.93                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             23.2%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/13 (0%)        0/14 (0%)        0/7 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              181                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.002 **       (e)              (e)              (e)              P=0.099                          | 
|POLY 3             |        P=0.002 **       (e)              (e)              (e)              P=0.090                          | 
|POLY 1.5           |        P=0.002 **       (e)              (e)              (e)              P=0.097                          | 
|POLY 6             |        P=0.002 **       (e)              (e)              (e)              P=0.082                          | 
|LOGISTIC REGRESSION|        P=0.019 *        (e)              (e)              (e)              P=0.277                          | 
|COCH-ARM / FISHERS |        P=0.003 **       (e)              (e)              (e)              P=0.112                          | 
|ORDER RESTRICTED   |        P=0.002 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain: Medulla                                                                                                                   | 
|     Neuronopathy                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        3/15 (20%)                       | 
|POLY-3 RATE (b)    |        0/13.88          0/14.62          0/14.15          0/14.62          3/14.02                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             21.4%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/12 (0%)        0/14 (0%)        1/9 (11%)                        | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              133                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.002 **       (e)              (e)              (e)              P=0.106                          | 
|POLY 3             |        P=0.002 **       (e)              (e)              (e)              P=0.106                          | 
|POLY 1.5           |        P=0.002 **       (e)              (e)              (e)              P=0.110                          | 
|POLY 6             |        P=0.002 **       (e)              (e)              (e)              P=0.101                          | 
|LOGISTIC REGRESSION|        P=0.007 **       (e)              (e)              (e)              P=0.099                          | 
|COCH-ARM / FISHERS |        P=0.003 **       (e)              (e)              (e)              P=0.112                          | 
|ORDER RESTRICTED   |        P=0.003 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 8       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain: Thalamus                                                                                                                  | 
|     Gliosis                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        2/15 (13%)                       | 
|POLY-3 RATE (b)    |        0/13.95          0/14.74          0/13.80          0/14.37          2/12.59                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             15.9%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/13 (0%)        0/14 (0%)        0/7 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              208                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.020 *        (e)              (e)              (e)              P=0.232                          | 
|POLY 3             |        P=0.017 *        (e)              (e)              (e)              P=0.207                          | 
|POLY 1.5           |        P=0.018 *        (e)              (e)              (e)              P=0.217                          | 
|POLY 6             |        P=0.016 *        (e)              (e)              (e)              P=0.194                          | 
|LOGISTIC REGRESSION|        P=0.065          (e)              (e)              (e)              P=0.475                          | 
|COCH-ARM / FISHERS |        P=0.021 *        (e)              (e)              (e)              P=0.241                          | 
|ORDER RESTRICTED   |        P=0.010 *        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain: Thalamus                                                                                                                  | 
|     Gliosis                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        1/15 (7%)                        | 
|POLY-3 RATE (b)    |        0/13.88          0/14.62          0/14.15          0/14.62          1/13.12                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             7.6%                             | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/12 (0%)        0/14 (0%)        0/9 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              186                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.138          (e)              (e)              (e)              P=0.500                          | 
|POLY 3             |        P=0.136          (e)              (e)              (e)              P=0.489                          | 
|POLY 1.5           |        P=0.139          (e)              (e)              (e)              P=0.495                          | 
|POLY 6             |        P=0.133          (e)              (e)              (e)              P=0.481                          | 
|LOGISTIC REGRESSION|        P=0.170          (e)              (e)              (e)              P=0.481                          | 
|COCH-ARM / FISHERS |        P=0.143          (e)              (e)              (e)              P=0.500                          | 
|ORDER RESTRICTED   |        P=0.079          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 9       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain: Thalamus                                                                                                                  | 
|     Neuronopathy                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        5/15 (33%)                       | 
|POLY-3 RATE (b)    |        0/13.95          0/14.74          0/13.80          0/14.37          5/13.56                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             36.9%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/13 (0%)        0/14 (0%)        0/7 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              181                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              (e)              P=0.022 *                        | 
|POLY 3             |        P<0.001 **       (e)              (e)              (e)              P=0.014 *                        | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              (e)              P=0.015 *                        | 
|POLY 6             |        P<0.001 **       (e)              (e)              (e)              P=0.012 *                        | 
|LOGISTIC REGRESSION|        P<0.001 **       (e)              (e)              (e)              P=0.077                          | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              (e)              P=0.021 *                        | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Brain: Thalamus                                                                                                                  | 
|     Neuronopathy                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        3/15 (20%)                       | 
|POLY-3 RATE (b)    |        0/13.88          0/14.62          0/14.15          0/14.62          3/14.61                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             20.5%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/12 (0%)        0/14 (0%)        0/9 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              133                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.003 **       (e)              (e)              (e)              P=0.124                          | 
|POLY 3             |        P=0.002 **       (e)              (e)              (e)              P=0.115                          | 
|POLY 1.5           |        P=0.002 **       (e)              (e)              (e)              P=0.115                          | 
|POLY 6             |        P=0.002 **       (e)              (e)              (e)              P=0.113                          | 
|LOGISTIC REGRESSION|        P=0.003 **       (e)              (e)              (e)              P=0.074                          | 
|COCH-ARM / FISHERS |        P=0.003 **       (e)              (e)              (e)              P=0.112                          | 
|ORDER RESTRICTED   |        P=0.003 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 10      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart: Myocardium                                                                                                                | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/15 (13%)       0/15 (0%)        0/15 (0%)        2/15 (13%)       0/15 (0%)                        | 
|POLY-3 RATE (b)    |        2/15.00          0/14.74          0/13.80          2/14.37          0/11.42                          | 
|POLY-3 PERCENT (g) |        13.3%            0.0%             0.0%             13.9%            0.0%                             | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/13 (0%)        2/14 (14%)       0/7 (0%)                         | 
|FIRST INCIDENCE    |        196              ---              ---              280 (T)          ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.453N         P=0.232N         P=0.247N         P=0.680N         P=0.285N                         | 
|POLY 3             |        P=0.420N         P=0.236N         P=0.251N         P=0.683          P=0.298N                         | 
|POLY 1.5           |        P=0.393N         P=0.234N         P=0.244N         P=0.689          P=0.268N                         | 
|POLY 6             |        P=0.452N         P=0.239N         P=0.257N         P=0.677          P=0.339N                         | 
|LOGISTIC REGRESSION|        P=0.243N         (e)              P=0.121N         P=0.667          P=0.049N*                        | 
|COCH-ARM / FISHERS |        P=0.358N         P=0.241N         P=0.241N         P=0.701N         P=0.241N                         | 
|ORDER RESTRICTED   |        P=0.129N         (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart: Myocardium                                                                                                                | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        0/13.88          0/14.62          0/14.15          0/14.62          0/12.41                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%                             | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/12 (0%)        0/14 (0%)        0/9 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)                              | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)                              | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)                              | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)                              | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)                              | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)                              | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 11      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart: Myocardium                                                                                                                | 
|     Mineralization                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        2/15 (13%)       1/15 (7%)        5/15 (33%)                       | 
|POLY-3 RATE (b)    |        0/13.95          0/14.74          2/14.66          1/14.37          5/13.21                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             13.6%            7.0%             37.9%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        1/13 (8%)        1/14 (7%)        0/7 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              146              280 (T)          208                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              P=0.240          P=0.515          P=0.019 *                        | 
|POLY 3             |        P<0.001 **       (e)              P=0.243          P=0.506          P=0.012 *                        | 
|POLY 1.5           |        P<0.001 **       (e)              P=0.238          P=0.503          P=0.014 *                        | 
|POLY 6             |        P<0.001 **       (e)              P=0.247          P=0.509          P=0.011 *                        | 
|LOGISTIC REGRESSION|        P=0.015 *        (e)              P=0.292          P=0.515          P=0.054                          | 
|COCH-ARM / FISHERS |        P=0.002 **       (e)              P=0.241          P=0.500          P=0.021 *                        | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart: Myocardium                                                                                                                | 
|     Mineralization                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        1/13.88          0/14.62          0/14.15          0/14.62          0/12.41                          | 
|POLY-3 PERCENT (g) |        7.2%             0.0%             0.0%             0.0%             0.0%                             | 
|TERMINAL (d)       |        1/13 (8%)        0/14 (0%)        0/12 (0%)        0/14 (0%)        0/9 (0%)                         | 
|FIRST INCIDENCE    |        281 (T)          ---              ---              ---              ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.397N         P=0.485N         P=0.516N         P=0.485N         P=0.573N                         | 
|POLY 3             |        P=0.342N         P=0.490N         P=0.496N         P=0.490N         P=0.522N                         | 
|POLY 1.5           |        P=0.353N         P=0.490N         P=0.494N         P=0.490N         P=0.512N                         | 
|POLY 6             |        P=0.329N         P=0.491N         P=0.501N         P=0.491N         P=0.534N                         | 
|LOGISTIC REGRESSION|        P=0.397N         (e)              (e)              (e)              (e)                              | 
|COCH-ARM / FISHERS |        P=0.361N         P=0.500N         P=0.500N         P=0.500N         P=0.500N                         | 
|ORDER RESTRICTED   |        P=0.107N         (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 12      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart: Myocardium                                                                                                                | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        2/15 (13%)                       | 
|POLY-3 RATE (b)    |        0/13.95          0/14.74          0/13.80          0/14.37          2/11.66                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             17.2%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/13 (0%)        0/14 (0%)        0/7 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              260                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.007 **       (e)              (e)              (e)              P=0.152                          | 
|POLY 3             |        P=0.016 *        (e)              (e)              (e)              P=0.190                          | 
|POLY 1.5           |        P=0.017 *        (e)              (e)              (e)              P=0.207                          | 
|POLY 6             |        P=0.015 *        (e)              (e)              (e)              P=0.171                          | 
|LOGISTIC REGRESSION|        P=0.018 *        (e)              (e)              (e)              P=0.189                          | 
|COCH-ARM / FISHERS |        P=0.021 *        (e)              (e)              (e)              P=0.241                          | 
|ORDER RESTRICTED   |        P=0.008 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart: Myocardium                                                                                                                | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        0/13.88          0/14.62          0/14.15          0/14.62          0/12.41                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%                             | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/12 (0%)        0/14 (0%)        0/9 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)                              | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)                              | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)                              | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)                              | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)                              | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)                              | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 13      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/15 (27%)       5/15 (33%)       5/15 (33%)       4/15 (27%)       4/15 (27%)                       | 
|POLY-3 RATE (b)    |        4/13.95          5/15.00          5/13.80          4/14.37          4/11.42                          | 
|POLY-3 PERCENT (g) |        28.7%            33.3%            36.2%            27.8%            35.0%                            | 
|TERMINAL (d)       |        4/13 (31%)       4/14 (29%)       5/13 (39%)       4/14 (29%)       4/7 (57%)                        | 
|FIRST INCIDENCE    |        280 (T)          253              280 (T)          280 (T)          280 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.261          P=0.556          P=0.500          P=0.615N         P=0.257                          | 
|POLY 3             |        P=0.512          P=0.551          P=0.493          P=0.639N         P=0.534                          | 
|POLY 1.5           |        P=0.549N         P=0.530          P=0.491          P=0.647N         P=0.590                          | 
|POLY 6             |        P=0.432          P=0.574          P=0.499          P=0.629N         P=0.455                          | 
|LOGISTIC REGRESSION|        P=0.380          P=0.534          P=0.500          P=0.615N         P=0.257                          | 
|COCH-ARM / FISHERS |        P=0.464N         P=0.500          P=0.500          P=0.659N         P=0.659N                         | 
|ORDER RESTRICTED   |        P=0.638          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        12/15 (80%)      12/15 (80%)      10/15 (67%)      14/15 (93%)      9/15 (60%)                       | 
|POLY-3 RATE (b)    |        12/14.86         12/15.00         10/14.15         14/15.00         9/13.49                          | 
|POLY-3 PERCENT (g) |        80.8%            80.0%            70.7%            93.3%            66.7%                            | 
|TERMINAL (d)       |        11/13 (85%)      11/14 (79%)      10/12 (83%)      13/14 (93%)      6/9 (67%)                        | 
|FIRST INCIDENCE    |        83               239              281 (T)          239              186                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.347          P=0.524N         P=0.470N         P=0.486          P=0.605                          | 
|POLY 3             |        P=0.348N         P=0.655N         P=0.420N         P=0.317          P=0.336N                         | 
|POLY 1.5           |        P=0.298N         P=0.662N         P=0.384N         P=0.308          P=0.294N                         | 
|POLY 6             |        P=0.378N         P=0.640N         P=0.472N         P=0.334          P=0.364N                         | 
|LOGISTIC REGRESSION|        P=0.245N         P=0.654          P=0.326N         P=0.280          P=0.226N                         | 
|COCH-ARM / FISHERS |        P=0.195N         P=0.674N         P=0.341N         P=0.299          P=0.213N                         | 
|ORDER RESTRICTED   |        P=0.292N         (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 14      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Accumulation, Hyaline Droplet                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        1/15 (7%)        0/15 (0%)        1/15 (7%)                        | 
|POLY-3 RATE (b)    |        0/13.95          0/14.74          1/14.14          0/14.37          1/11.62                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             7.1%             0.0%             8.6%                             | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/13 (0%)        0/14 (0%)        0/7 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              244              ---              260                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.228          (e)              P=0.515          (e)              P=0.427                          | 
|POLY 3             |        P=0.263          (e)              P=0.503          (e)              P=0.464                          | 
|POLY 1.5           |        P=0.281          (e)              P=0.500          (e)              P=0.479                          | 
|POLY 6             |        P=0.244          (e)              P=0.508          (e)              P=0.444                          | 
|LOGISTIC REGRESSION|        P=0.382          (e)              P=0.538          (e)              P=0.506                          | 
|COCH-ARM / FISHERS |        P=0.306          (e)              P=0.500          (e)              P=0.500                          | 
|ORDER RESTRICTED   |        P=0.185          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Accumulation, Hyaline Droplet                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        2/15 (13%)       1/15 (7%)        3/15 (20%)                       | 
|POLY-3 RATE (b)    |        0/13.88          0/14.62          2/14.59          1/14.62          3/13.48                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             13.7%            6.8%             22.3%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        1/12 (8%)        1/14 (7%)        0/9 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              232              281 (T)          186                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.022 *        (e)              P=0.238          P=0.515          P=0.100                          | 
|POLY 3             |        P=0.030 *        (e)              P=0.243          P=0.510          P=0.099                          | 
|POLY 1.5           |        P=0.032 *        (e)              P=0.242          P=0.510          P=0.103                          | 
|POLY 6             |        P=0.029 *        (e)              P=0.241          P=0.509          P=0.096                          | 
|LOGISTIC REGRESSION|        P=0.054          (e)              P=0.201          P=0.515          P=0.117                          | 
|COCH-ARM / FISHERS |        P=0.035 *        (e)              P=0.241          P=0.500          P=0.112                          | 
|ORDER RESTRICTED   |        P=0.026 *        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 15      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Angiectasis Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        1/15 (7%)                        | 
|POLY-3 RATE (b)    |        0/13.95          0/14.74          0/13.80          0/14.37          1/11.42                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             8.8%                             | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/13 (0%)        0/14 (0%)        1/7 (14%)                        | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              280 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.074          (e)              (e)              (e)              P=0.377                          | 
|POLY 3             |        P=0.123          (e)              (e)              (e)              P=0.460                          | 
|POLY 1.5           |        P=0.132          (e)              (e)              (e)              P=0.478                          | 
|POLY 6             |        P=0.114          (e)              (e)              (e)              P=0.437                          | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              P=0.377                          | 
|COCH-ARM / FISHERS |        P=0.143          (e)              (e)              (e)              P=0.500                          | 
|ORDER RESTRICTED   |        P=0.061          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Angiectasis Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        1/15 (7%)        2/15 (13%)                       | 
|POLY-3 RATE (b)    |        0/13.88          0/14.62          0/14.15          1/14.62          2/12.44                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             6.8%             16.1%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/12 (0%)        1/14 (7%)        1/9 (11%)                        | 
|FIRST INCIDENCE    |        ---              ---              ---              281 (T)          278                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.015 *        (e)              (e)              P=0.515          P=0.183                          | 
|POLY 3             |        P=0.023 *        (e)              (e)              P=0.510          P=0.205                          | 
|POLY 1.5           |        P=0.025 *        (e)              (e)              P=0.510          P=0.217                          | 
|POLY 6             |        P=0.021 *        (e)              (e)              P=0.509          P=0.194                          | 
|LOGISTIC REGRESSION|        P=0.018 *        (e)              (e)              P=0.515          P=0.188                          | 
|COCH-ARM / FISHERS |        P=0.030 *        (e)              (e)              P=0.500          P=0.241                          | 
|ORDER RESTRICTED   |        P=0.033 *        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 16      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        1/15 (7%)        0/15 (0%)        2/15 (13%)       1/15 (7%)                        | 
|POLY-3 RATE (b)    |        0/13.95          1/14.74          0/13.80          2/14.37          1/11.95                          | 
|POLY-3 PERCENT (g) |        0.0%             6.8%             0.0%             13.9%            8.4%                             | 
|TERMINAL (d)       |        0/13 (0%)        1/14 (7%)        0/13 (0%)        2/14 (14%)       0/7 (0%)                         | 
|FIRST INCIDENCE    |        ---              280 (T)          ---              280 (T)          217                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.171          P=0.515          (e)              P=0.252          P=0.469                          | 
|POLY 3             |        P=0.224          P=0.511          (e)              P=0.238          P=0.469                          | 
|POLY 1.5           |        P=0.254          P=0.507          (e)              P=0.235          P=0.482                          | 
|POLY 6             |        P=0.190          P=0.515          (e)              P=0.242          P=0.452                          | 
|LOGISTIC REGRESSION|        P=0.322          P=0.515          (e)              P=0.252          P=0.688                          | 
|COCH-ARM / FISHERS |        P=0.293          P=0.500          (e)              P=0.241          P=0.500                          | 
|ORDER RESTRICTED   |        P=0.198          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/15 (13%)       3/15 (20%)       1/15 (7%)        1/15 (7%)        2/15 (13%)                       | 
|POLY-3 RATE (b)    |        2/13.88          3/14.62          1/14.15          1/14.62          2/12.44                          | 
|POLY-3 PERCENT (g) |        14.4%            20.5%            7.1%             6.8%             16.1%                            | 
|TERMINAL (d)       |        2/13 (15%)       3/14 (21%)       1/12 (8%)        1/14 (7%)        1/9 (11%)                        | 
|FIRST INCIDENCE    |        281 (T)          281 (T)          281 (T)          281 (T)          278                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.567          P=0.536          P=0.529N         P=0.473N         P=0.577                          | 
|POLY 3             |        P=0.521N         P=0.524          P=0.493N         P=0.482N         P=0.659                          | 
|POLY 1.5           |        P=0.512N         P=0.523          P=0.489N         P=0.483N         P=0.679                          | 
|POLY 6             |        P=0.528N         P=0.522          P=0.502N         P=0.484N         P=0.638                          | 
|LOGISTIC REGRESSION|        P=0.596N         P=0.536          P=0.529N         P=0.473N         P=0.626                          | 
|COCH-ARM / FISHERS |        P=0.500N         P=0.500          P=0.500N         P=0.500N         P=0.701N                         | 
|ORDER RESTRICTED   |        P=0.494N         (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 17      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Infiltration Cellular Lymphoid                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        2/15 (13%)       0/15 (0%)        2/15 (13%)       1/15 (7%)                        | 
|POLY-3 RATE (b)    |        1/14.34          2/14.74          0/13.80          2/14.37          1/11.42                          | 
|POLY-3 PERCENT (g) |        7.0%             13.6%            0.0%             13.9%            8.8%                             | 
|TERMINAL (d)       |        0/13 (0%)        2/14 (14%)       0/13 (0%)        2/14 (14%)       1/7 (14%)                        | 
|FIRST INCIDENCE    |        237              280 (T)          ---              280 (T)          280 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.441          P=0.525          P=0.500N         P=0.517          P=0.651                          | 
|POLY 3             |        P=0.514          P=0.510          P=0.508N         P=0.501          P=0.708                          | 
|POLY 1.5           |        P=0.560          P=0.507          P=0.505N         P=0.501          P=0.732                          | 
|POLY 6             |        P=0.456          P=0.511          P=0.510N         P=0.500          P=0.674                          | 
|LOGISTIC REGRESSION|        P=0.580          P=0.414          P=0.448N         P=0.483          P=0.768N                         | 
|COCH-ARM / FISHERS |        P=0.618          P=0.500          P=0.500N         P=0.500          P=0.759N                         | 
|ORDER RESTRICTED   |        P=0.596          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Infiltration Cellular Lymphoid                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        3/15 (20%)       1/15 (7%)        1/15 (7%)        1/15 (7%)                        | 
|POLY-3 RATE (b)    |        0/13.88          3/14.62          1/14.15          1/14.62          1/12.41                          | 
|POLY-3 PERCENT (g) |        0.0%             20.5%            7.1%             6.8%             8.1%                             | 
|TERMINAL (d)       |        0/13 (0%)        3/14 (21%)       1/12 (8%)        1/14 (7%)        1/9 (11%)                        | 
|FIRST INCIDENCE    |        ---              281 (T)          281 (T)          281 (T)          281 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.569          P=0.128          P=0.484          P=0.515          P=0.427                          | 
|POLY 3             |        P=0.581N         P=0.115          P=0.504          P=0.510          P=0.478                          | 
|POLY 1.5           |        P=0.569N         P=0.115          P=0.506          P=0.510          P=0.488                          | 
|POLY 6             |        P=0.593N         P=0.114          P=0.499          P=0.509          P=0.466                          | 
|LOGISTIC REGRESSION|        (e)              P=0.128          P=0.484          P=0.515          P=0.427                          | 
|COCH-ARM / FISHERS |        P=0.560N         P=0.112          P=0.500          P=0.500          P=0.500                          | 
|ORDER RESTRICTED   |        P=0.295          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 18      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        6/15 (40%)       9/15 (60%)       8/15 (53%)       9/15 (60%)       2/15 (13%)                       | 
|POLY-3 RATE (b)    |        6/13.95          9/14.74          8/13.80          9/15.00          2/11.95                          | 
|POLY-3 PERCENT (g) |        43.0%            61.1%            58.0%            60.0%            16.7%                            | 
|TERMINAL (d)       |        6/13 (46%)       9/14 (64%)       8/13 (62%)       8/14 (57%)       1/7 (14%)                        | 
|FIRST INCIDENCE    |        280 (T)          280 (T)          280 (T)          201              217                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.263N         P=0.291          P=0.350          P=0.304          P=0.361N                         | 
|POLY 3             |        P=0.070N         P=0.278          P=0.343          P=0.296          P=0.152N                         | 
|POLY 1.5           |        P=0.046N*        P=0.261          P=0.344          P=0.270          P=0.129N                         | 
|POLY 6             |        P=0.111N         P=0.295          P=0.350          P=0.329          P=0.188N                         | 
|LOGISTIC REGRESSION|        P=0.084N         P=0.291          P=0.350          P=0.241          P=0.185N                         | 
|COCH-ARM / FISHERS |        P=0.030N*        P=0.233          P=0.358          P=0.233          P=0.107N                         | 
|ORDER RESTRICTED   |        P=0.036N*        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        11/15 (73%)      10/15 (67%)      8/15 (53%)       8/15 (53%)       7/15 (47%)                       | 
|POLY-3 RATE (b)    |        11/13.88         10/15.00         8/14.15          8/14.62          7/12.44                          | 
|POLY-3 PERCENT (g) |        79.2%            66.7%            56.5%            54.7%            56.3%                            | 
|TERMINAL (d)       |        11/13 (85%)      9/14 (64%)       8/12 (67%)       8/14 (57%)       6/9 (67%)                        | 
|FIRST INCIDENCE    |        281 (T)          239              281 (T)          281 (T)          278                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.418N         P=0.379N         P=0.285N         P=0.132N         P=0.531N                         | 
|POLY 3             |        P=0.167N         P=0.370N         P=0.184N         P=0.158N         P=0.191N                         | 
|POLY 1.5           |        P=0.132N         P=0.394N         P=0.179N         P=0.165N         P=0.149N                         | 
|POLY 6             |        P=0.207N         P=0.351N         P=0.206N         P=0.160N         P=0.248N                         | 
|LOGISTIC REGRESSION|        P=0.232N         P=0.410N         P=0.285N         P=0.132N         P=0.307N                         | 
|COCH-ARM / FISHERS |        P=0.092N         P=0.500N         P=0.225N         P=0.225N         P=0.132N                         | 
|ORDER RESTRICTED   |        P=0.184N         (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 19      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Necrosis Focal                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        2/15 (13%)       2/15 (13%)       0/15 (0%)        5/15 (33%)                       | 
|POLY-3 RATE (b)    |        1/14.61          2/15.00          2/15.00          0/14.37          5/13.56                          | 
|POLY-3 PERCENT (g) |        6.9%             13.3%            13.3%            0.0%             36.9%                            | 
|TERMINAL (d)       |        0/13 (0%)        1/14 (7%)        0/13 (0%)        0/14 (0%)        0/7 (0%)                         | 
|FIRST INCIDENCE    |        196              253              146              ---              181                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.028 *        P=0.525          P=0.501          P=0.500N         P=0.075                          | 
|POLY 3             |        P=0.035 *        P=0.509          P=0.509          P=0.503N         P=0.062                          | 
|POLY 1.5           |        P=0.038 *        P=0.505          P=0.505          P=0.502N         P=0.069                          | 
|POLY 6             |        P=0.033 *        P=0.515          P=0.515          P=0.503N         P=0.054                          | 
|LOGISTIC REGRESSION|        P=0.452          P=0.170          P=0.381          (e)              P=0.349                          | 
|COCH-ARM / FISHERS |        P=0.046 *        P=0.500          P=0.500          P=0.500N         P=0.084                          | 
|ORDER RESTRICTED   |        P=0.013 *        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Necrosis Focal                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        5/15 (33%)       2/15 (13%)       2/15 (13%)                       | 
|POLY-3 RATE (b)    |        0/13.88          0/14.62          5/14.98          2/14.62          2/13.46                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             33.4%            13.7%            14.9%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        3/12 (25%)       2/14 (14%)       0/9 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              232              281 (T)          186                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.182          (e)              P=0.030 *        P=0.252          P=0.223                          | 
|POLY 3             |        P=0.231          (e)              P=0.022 *        P=0.243          P=0.223                          | 
|POLY 1.5           |        P=0.243          (e)              P=0.021 *        P=0.243          P=0.228                          | 
|POLY 6             |        P=0.223          (e)              P=0.023 *        P=0.242          P=0.219                          | 
|LOGISTIC REGRESSION|        P=0.324          (e)              P=0.019 *        P=0.252          P=0.231                          | 
|COCH-ARM / FISHERS |        P=0.265          (e)              P=0.021 *        P=0.241          P=0.241                          | 
|ORDER RESTRICTED   |        P=0.070          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 20      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        3/15 (20%)       7/15 (47%)       5/15 (33%)       4/15 (27%)       2/15 (13%)                       | 
|POLY-3 RATE (b)    |        3/13.95          7/14.74          5/13.80          4/14.37          2/11.42                          | 
|POLY-3 PERCENT (g) |        21.5%            47.5%            36.2%            27.8%            17.5%                            | 
|TERMINAL (d)       |        3/13 (23%)       7/14 (50%)       5/13 (39%)       4/14 (29%)       2/7 (29%)                        | 
|FIRST INCIDENCE    |        280 (T)          280 (T)          280 (T)          280 (T)          280 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.442N         P=0.152          P=0.338          P=0.545          P=0.604                          | 
|POLY 3             |        P=0.230N         P=0.141          P=0.334          P=0.518          P=0.596N                         | 
|POLY 1.5           |        P=0.187N         P=0.133          P=0.334          P=0.510          P=0.554N                         | 
|POLY 6             |        P=0.287N         P=0.149          P=0.338          P=0.528          P=0.650N                         | 
|LOGISTIC REGRESSION|        P=0.442N         P=0.152          P=0.338          P=0.545          P=0.604                          | 
|COCH-ARM / FISHERS |        P=0.138N         P=0.123          P=0.341          P=0.500          P=0.500N                         | 
|ORDER RESTRICTED   |        P=0.307N         (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        8/15 (53%)       8/15 (53%)       7/15 (47%)       5/15 (33%)       3/15 (20%)                       | 
|POLY-3 RATE (b)    |        8/13.88          8/15.00          7/14.15          5/14.62          3/12.44                          | 
|POLY-3 PERCENT (g) |        57.6%            53.3%            49.5%            34.2%            24.1%                            | 
|TERMINAL (d)       |        8/13 (62%)       7/14 (50%)       7/12 (58%)       5/14 (36%)       2/9 (22%)                        | 
|FIRST INCIDENCE    |        281 (T)          239              281 (T)          281 (T)          278                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.081N         P=0.558N         P=0.595N         P=0.174N         P=0.206N                         | 
|POLY 3             |        P=0.033N*        P=0.555N         P=0.479N         P=0.191N         P=0.083N                         | 
|POLY 1.5           |        P=0.026N*        P=0.571N         P=0.467N         P=0.194N         P=0.068N                         | 
|POLY 6             |        P=0.042N*        P=0.543N         P=0.508N         P=0.193N         P=0.102N                         | 
|LOGISTIC REGRESSION|        P=0.040N*        P=0.592N         P=0.595N         P=0.174N         P=0.125N                         | 
|COCH-ARM / FISHERS |        P=0.019N*        P=0.642N         P=0.500N         P=0.231N         P=0.064N                         | 
|ORDER RESTRICTED   |        P=0.070N         (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 21      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolar Epithelium                                                                                                        | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        2/15 (13%)       0/15 (0%)        2/15 (13%)       2/15 (13%)                       | 
|POLY-3 RATE (b)    |        0/13.95          2/14.74          0/13.80          2/14.37          2/11.42                          | 
|POLY-3 PERCENT (g) |        0.0%             13.6%            0.0%             13.9%            17.5%                            | 
|TERMINAL (d)       |        0/13 (0%)        2/14 (14%)       0/13 (0%)        2/14 (14%)       2/7 (29%)                        | 
|FIRST INCIDENCE    |        ---              280 (T)          ---              280 (T)          280 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.056          P=0.252          (e)              P=0.252          P=0.112                          | 
|POLY 3             |        P=0.128          P=0.244          (e)              P=0.238          P=0.186                          | 
|POLY 1.5           |        P=0.150          P=0.239          (e)              P=0.235          P=0.205                          | 
|POLY 6             |        P=0.103          P=0.249          (e)              P=0.242          P=0.163                          | 
|LOGISTIC REGRESSION|        (e)              P=0.252          (e)              P=0.252          P=0.112                          | 
|COCH-ARM / FISHERS |        P=0.183          P=0.241          (e)              P=0.241          P=0.241                          | 
|ORDER RESTRICTED   |        P=0.110          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Alveolar Epithelium                                                                                                        | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        2/15 (13%)       1/15 (7%)        0/15 (0%)        1/15 (7%)                        | 
|POLY-3 RATE (b)    |        1/13.88          2/14.62          1/14.15          0/14.62          1/12.41                          | 
|POLY-3 PERCENT (g) |        7.2%             13.7%            7.1%             0.0%             8.1%                             | 
|TERMINAL (d)       |        1/13 (8%)        2/14 (14%)       1/12 (8%)        0/14 (0%)        1/9 (11%)                        | 
|FIRST INCIDENCE    |        281 (T)          281 (T)          281 (T)          ---              281 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.544N         P=0.527          P=0.747          P=0.485N         P=0.680                          | 
|POLY 3             |        P=0.437N         P=0.518          P=0.757N         P=0.490N         P=0.736                          | 
|POLY 1.5           |        P=0.435N         P=0.517          P=0.754N         P=0.490N         P=0.748                          | 
|POLY 6             |        P=0.438N         P=0.516          P=0.760          P=0.491N         P=0.722                          | 
|LOGISTIC REGRESSION|        P=0.544N         P=0.527          P=0.747          (e)              P=0.680                          | 
|COCH-ARM / FISHERS |        P=0.435N         P=0.500          P=0.759N         P=0.500N         P=0.759N                         | 
|ORDER RESTRICTED   |        P=0.452N         (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 22      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        2/15 (13%)       0/15 (0%)        1/15 (7%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        0/13.95          2/14.74          0/13.80          1/14.37          0/11.42                          | 
|POLY-3 PERCENT (g) |        0.0%             13.6%            0.0%             7.0%             0.0%                             | 
|TERMINAL (d)       |        0/13 (0%)        2/14 (14%)       0/13 (0%)        1/14 (7%)        0/7 (0%)                         | 
|FIRST INCIDENCE    |        ---              280 (T)          ---              280 (T)          ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.551N         P=0.252          (e)              P=0.515          (e)                              | 
|POLY 3             |        P=0.450N         P=0.244          (e)              P=0.506          (e)                              | 
|POLY 1.5           |        P=0.436N         P=0.239          (e)              P=0.503          (e)                              | 
|POLY 6             |        P=0.467N         P=0.249          (e)              P=0.509          (e)                              | 
|LOGISTIC REGRESSION|        (e)              P=0.252          (e)              P=0.515          (e)                              | 
|COCH-ARM / FISHERS |        P=0.417N         P=0.241          (e)              P=0.500          (e)                              | 
|ORDER RESTRICTED   |        P=0.360N         (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        1/15 (7%)                        | 
|POLY-3 RATE (b)    |        1/13.88          0/14.62          0/14.15          0/14.62          1/12.41                          | 
|POLY-3 PERCENT (g) |        7.2%             0.0%             0.0%             0.0%             8.1%                             | 
|TERMINAL (d)       |        1/13 (8%)        0/14 (0%)        0/12 (0%)        0/14 (0%)        1/9 (11%)                        | 
|FIRST INCIDENCE    |        281 (T)          ---              ---              ---              281 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.430          P=0.485N         P=0.516N         P=0.485N         P=0.680                          | 
|POLY 3             |        P=0.478          P=0.490N         P=0.496N         P=0.490N         P=0.736                          | 
|POLY 1.5           |        P=0.484          P=0.490N         P=0.494N         P=0.490N         P=0.748                          | 
|POLY 6             |        P=0.474          P=0.491N         P=0.501N         P=0.491N         P=0.722                          | 
|LOGISTIC REGRESSION|        P=0.430          (e)              (e)              (e)              P=0.680                          | 
|COCH-ARM / FISHERS |        P=0.500          P=0.500N         P=0.500N         P=0.500N         P=0.759N                         | 
|ORDER RESTRICTED   |        P=0.305          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 23      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        2/15 (13%)       0/15 (0%)        1/14 (7%)        1/15 (7%)                        | 
|POLY-3 RATE (b)    |        0/13.95          2/14.74          0/13.80          1/14.00          1/11.42                          | 
|POLY-3 PERCENT (g) |        0.0%             13.6%            0.0%             7.1%             8.8%                             | 
|TERMINAL (d)       |        0/13 (0%)        2/14 (14%)       0/13 (0%)        1/14 (7%)        1/7 (14%)                        | 
|FIRST INCIDENCE    |        ---              280 (T)          ---              280 (T)          280 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.334          P=0.252          (e)              P=0.515          P=0.377                          | 
|POLY 3             |        P=0.424          P=0.244          (e)              P=0.501          P=0.460                          | 
|POLY 1.5           |        P=0.455          P=0.239          (e)              P=0.495          P=0.478                          | 
|POLY 6             |        P=0.385          P=0.249          (e)              P=0.507          P=0.437                          | 
|LOGISTIC REGRESSION|        (e)              P=0.252          (e)              P=0.515          P=0.377                          | 
|COCH-ARM / FISHERS |        P=0.496          P=0.241          (e)              P=0.483          P=0.500                          | 
|ORDER RESTRICTED   |        P=0.326          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        1/15 (7%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        0/13.88          0/14.62          0/14.15          1/14.62          0/12.41                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             6.8%             0.0%                             | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/12 (0%)        1/14 (7%)        0/9 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              281 (T)          ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.603          (e)              (e)              P=0.515          (e)                              | 
|POLY 3             |        P=0.560          (e)              (e)              P=0.510          (e)                              | 
|POLY 1.5           |        P=0.591          (e)              (e)              P=0.510          (e)                              | 
|POLY 6             |        P=0.529          (e)              (e)              P=0.509          (e)                              | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.515          (e)                              | 
|COCH-ARM / FISHERS |        P=0.639          (e)              (e)              P=0.500          (e)                              | 
|ORDER RESTRICTED   |        P=0.388          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 24      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node: Mediastinal                                                                                                          | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/14 (0%)        1/14 (7%)        0/15 (0%)        0/13 (0%)        0/13 (0%)                        | 
|POLY-3 RATE (b)    |        0/12.95          1/13.74          0/13.80          0/12.37          0/9.42                           | 
|POLY-3 PERCENT (g) |        0.0%             7.3%             0.0%             0.0%             0.0%                             | 
|TERMINAL (d)       |        0/12 (0%)        1/13 (8%)        0/13 (0%)        0/12 (0%)        0/5 (0%)                         | 
|FIRST INCIDENCE    |        ---              280 (T)          ---              ---              ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.620N         P=0.516          (e)              (e)              (e)                              | 
|POLY 3             |        P=0.469N         P=0.512          (e)              (e)              (e)                              | 
|POLY 1.5           |        P=0.491N         P=0.507          (e)              (e)              (e)                              | 
|POLY 6             |        P=0.435N         P=0.516          (e)              (e)              (e)                              | 
|LOGISTIC REGRESSION|        (e)              P=0.516          (e)              (e)              (e)                              | 
|COCH-ARM / FISHERS |        P=0.515N         P=0.500          (e)              (e)              (e)                              | 
|ORDER RESTRICTED   |        P=0.455N         (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node: Mediastinal                                                                                                          | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/13 (15%)       1/15 (7%)        0/15 (0%)        0/13 (0%)        0/14 (0%)                        | 
|POLY-3 RATE (b)    |        2/11.88          1/14.62          0/14.15          0/12.62          0/11.41                          | 
|POLY-3 PERCENT (g) |        16.8%            6.8%             0.0%             0.0%             0.0%                             | 
|TERMINAL (d)       |        2/11 (18%)       1/14 (7%)        0/12 (0%)        0/12 (0%)        0/8 (0%)                         | 
|FIRST INCIDENCE    |        281 (T)          281 (T)          ---              ---              ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.130N         P=0.413N         P=0.216N         P=0.216N         P=0.307N                         | 
|POLY 3             |        P=0.101N         P=0.426N         P=0.190N         P=0.216N         P=0.238N                         | 
|POLY 1.5           |        P=0.104N         P=0.428N         P=0.189N         P=0.217N         P=0.225N                         | 
|POLY 6             |        P=0.098N         P=0.428N         P=0.195N         P=0.217N         P=0.253N                         | 
|LOGISTIC REGRESSION|        P=0.130N         P=0.413N         (e)              (e)              (e)                              | 
|COCH-ARM / FISHERS |        P=0.106N         P=0.444N         P=0.206N         P=0.240N         P=0.222N                         | 
|ORDER RESTRICTED   |        P=0.047N*        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 25      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                                                                                                             | 
|POLY-3 RATE (b)    |                                                                                                             | 
|POLY-3 PERCENT (g) |                                                                                                             | 
|TERMINAL (d)       |                                                                                                             | 
|FIRST INCIDENCE    |                                                                                                             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                                                                                                             | 
|POLY 3             |                                                                                                             | 
|POLY 1.5           |                                                                                                             | 
|POLY 6             |                                                                                                             | 
|LOGISTIC REGRESSION|                                                                                                             | 
|COCH-ARM / FISHERS |                                                                                                             | 
|ORDER RESTRICTED   |                                                                                                             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/15 (27%)       0/15 (0%)        0/15 (0%)        0/15 (0%)        2/15 (13%)                       | 
|POLY-3 RATE (b)    |        4/13.88          0/14.62          0/14.15          0/14.62          2/13.12                          | 
|POLY-3 PERCENT (g) |        28.8%            0.0%             0.0%             0.0%             15.2%                            | 
|TERMINAL (d)       |        4/13 (31%)       0/14 (0%)        0/12 (0%)        0/14 (0%)        1/9 (11%)                        | 
|FIRST INCIDENCE    |        281 (T)          ---              ---              ---              186                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.603N         P=0.047N*        P=0.064N         P=0.047N*        P=0.484N                         | 
|POLY 3             |        P=0.504N         P=0.038N*        P=0.042N*        P=0.038N*        P=0.353N                         | 
|POLY 1.5           |        P=0.508N         P=0.039N*        P=0.041N*        P=0.039N*        P=0.337N                         | 
|POLY 6             |        P=0.496N         P=0.039N*        P=0.044N*        P=0.039N*        P=0.372N                         | 
|LOGISTIC REGRESSION|        P=0.477N         (e)              (e)              (e)              P=0.330N                         | 
|COCH-ARM / FISHERS |        P=0.500N         P=0.050N         P=0.050N         P=0.050N         P=0.326N                         | 
|ORDER RESTRICTED   |        P=0.011N*        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 26      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        0/13.95          0/14.74          0/12.80          0/14.37          0/11.42                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%                             | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/12 (0%)        0/14 (0%)        0/7 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)                              | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)                              | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)                              | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)                              | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)                              | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)                              | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Distalis                                                                                                   | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        1/15 (7%)        2/15 (13%)       1/15 (7%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        1/13.88          1/14.62          2/14.15          1/14.62          0/12.41                          | 
|POLY-3 PERCENT (g) |        7.2%             6.8%             14.1%            6.8%             0.0%                             | 
|TERMINAL (d)       |        1/13 (8%)        1/14 (7%)        2/12 (17%)       1/14 (7%)        0/9 (0%)                         | 
|FIRST INCIDENCE    |        281 (T)          281 (T)          281 (T)          281 (T)          ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.335N         P=0.748N         P=0.471          P=0.748N         P=0.573N                         | 
|POLY 3             |        P=0.290N         P=0.749N         P=0.507          P=0.749N         P=0.522N                         | 
|POLY 1.5           |        P=0.277N         P=0.750N         P=0.511          P=0.750N         P=0.512N                         | 
|POLY 6             |        P=0.303N         P=0.751N         P=0.498          P=0.751N         P=0.534N                         | 
|LOGISTIC REGRESSION|        P=0.335N         P=0.748N         P=0.471          P=0.748N         (e)                              | 
|COCH-ARM / FISHERS |        P=0.256N         P=0.759N         P=0.500          P=0.759N         P=0.500N                         | 
|ORDER RESTRICTED   |        P=0.328N         (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 27      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        1/15 (7%)        2/15 (13%)                       | 
|POLY-3 RATE (b)    |        0/13.95          0/14.74          0/13.80          1/15.00          2/12.48                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             6.7%             16.0%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/13 (0%)        0/14 (0%)        0/7 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              201              217                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.023 *        (e)              (e)              P=0.514          P=0.197                          | 
|POLY 3             |        P=0.023 *        (e)              (e)              P=0.514          P=0.205                          | 
|POLY 1.5           |        P=0.026 *        (e)              (e)              P=0.509          P=0.216                          | 
|POLY 6             |        P=0.020 *        (e)              (e)              P=0.521          P=0.192                          | 
|LOGISTIC REGRESSION|        P=0.109          (e)              (e)              P=0.425          P=0.434                          | 
|COCH-ARM / FISHERS |        P=0.030 *        (e)              (e)              P=0.500          P=0.241                          | 
|ORDER RESTRICTED   |        P=0.033 *        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        0/13.88          0/14.62          0/14.15          0/14.62          0/12.41                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%                             | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/12 (0%)        0/14 (0%)        0/9 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)                              | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)                              | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)                              | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)                              | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)                              | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)                              | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 28      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/15 (27%)       7/15 (47%)       7/15 (47%)       5/15 (33%)       5/15 (33%)                       | 
|POLY-3 RATE (b)    |        4/15.00          7/15.00          7/15.00          5/14.37          5/12.79                          | 
|POLY-3 PERCENT (g) |        26.7%            46.7%            46.7%            34.8%            39.1%                            | 
|TERMINAL (d)       |        2/13 (15%)       6/14 (43%)       5/13 (39%)       5/14 (36%)       2/7 (29%)                        | 
|FIRST INCIDENCE    |        196              253              146              280 (T)          208                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.283          P=0.295          P=0.256          P=0.538          P=0.283                          | 
|POLY 3             |        P=0.504          P=0.227          P=0.227          P=0.470          P=0.388                          | 
|POLY 1.5           |        P=0.557N         P=0.227          P=0.227          P=0.482          P=0.434                          | 
|POLY 6             |        P=0.429          P=0.227          P=0.227          P=0.459          P=0.335                          | 
|LOGISTIC REGRESSION|        P=0.291N         (e)              (e)              P=0.464          P=0.625N                         | 
|COCH-ARM / FISHERS |        P=0.466N         P=0.225          P=0.225          P=0.500          P=0.500                          | 
|ORDER RESTRICTED   |        P=0.372          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        9/15 (60%)       5/15 (33%)       10/15 (67%)      10/15 (67%)      10/15 (67%)                      | 
|POLY-3 RATE (b)    |        9/15.00          5/15.00          10/15.00         10/14.62         10/14.41                         | 
|POLY-3 PERCENT (g) |        60.0%            33.3%            66.7%            68.4%            69.4%                            | 
|TERMINAL (d)       |        7/13 (54%)       4/14 (29%)       7/12 (58%)       10/14 (71%)      5/9 (56%)                        | 
|FIRST INCIDENCE    |        83               239              232              281 (T)          133                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.046 *        P=0.135N         P=0.434          P=0.585          P=0.235                          | 
|POLY 3             |        P=0.134          P=0.136N         P=0.500          P=0.463          P=0.442                          | 
|POLY 1.5           |        P=0.152          P=0.136N         P=0.500          P=0.480          P=0.465                          | 
|POLY 6             |        P=0.117          P=0.136N         P=0.500          P=0.440          P=0.418                          | 
|LOGISTIC REGRESSION|        P=0.254          (e)              (e)              P=0.468          P=0.574                          | 
|COCH-ARM / FISHERS |        P=0.181          P=0.136N         P=0.500          P=0.500          P=0.500                          | 
|ORDER RESTRICTED   |        P=0.169          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 29      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Ulcer                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        1/15 (7%)        0/15 (0%)        0/15 (0%)        3/15 (20%)                       | 
|POLY-3 RATE (b)    |        0/13.95          1/15.00          0/13.80          0/14.37          3/12.19                          | 
|POLY-3 PERCENT (g) |        0.0%             6.7%             0.0%             0.0%             24.6%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/13 (0%)        0/14 (0%)        1/7 (14%)                        | 
|FIRST INCIDENCE    |        ---              253              ---              ---              181                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.009 **       P=0.529          (e)              (e)              P=0.066                          | 
|POLY 3             |        P=0.017 *        P=0.514          (e)              (e)              P=0.080                          | 
|POLY 1.5           |        P=0.018 *        P=0.509          (e)              (e)              P=0.091                          | 
|POLY 6             |        P=0.017 *        P=0.521          (e)              (e)              P=0.067                          | 
|LOGISTIC REGRESSION|        P=0.054          P=0.372          (e)              (e)              P=0.155                          | 
|COCH-ARM / FISHERS |        P=0.023 *        P=0.500          (e)              (e)              P=0.112                          | 
|ORDER RESTRICTED   |        P=0.005 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Ulcer                                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        0/13.88          0/14.62          0/14.15          0/14.62          0/12.41                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%                             | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/12 (0%)        0/14 (0%)        0/9 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)                              | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)                              | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)                              | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)                              | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)                              | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)                              | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 30      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach: Epithelium                                                                                                 | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        1/15 (7%)        1/15 (7%)        0/15 (0%)        6/15 (40%)                       | 
|POLY-3 RATE (b)    |        0/13.95          1/15.00          1/14.14          0/14.37          6/13.56                          | 
|POLY-3 PERCENT (g) |        0.0%             6.7%             7.1%             0.0%             44.3%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/13 (0%)        0/14 (0%)        1/7 (14%)                        | 
|FIRST INCIDENCE    |        ---              253              244              ---              181                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.529          P=0.515          (e)              P=0.009 **                       | 
|POLY 3             |        P<0.001 **       P=0.514          P=0.503          (e)              P=0.004 **                       | 
|POLY 1.5           |        P<0.001 **       P=0.509          P=0.500          (e)              P=0.004 **                       | 
|POLY 6             |        P<0.001 **       P=0.521          P=0.508          (e)              P=0.003 **                       | 
|LOGISTIC REGRESSION|        P=0.005 **       P=0.372          P=0.538          (e)              P=0.031 *                        | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.500          P=0.500          (e)              P=0.008 **                       | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach: Epithelium                                                                                                 | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        1/15 (7%)        4/15 (27%)                       | 
|POLY-3 RATE (b)    |        0/13.88          0/14.62          0/14.15          1/14.62          4/13.12                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             6.8%             30.5%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/12 (0%)        1/14 (7%)        3/9 (33%)                        | 
|FIRST INCIDENCE    |        ---              ---              ---              281 (T)          186                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.515          P=0.031 *                        | 
|POLY 3             |        P<0.001 **       (e)              (e)              P=0.510          P=0.037 *                        | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P=0.510          P=0.041 *                        | 
|POLY 6             |        P<0.001 **       (e)              (e)              P=0.509          P=0.033 *                        | 
|LOGISTIC REGRESSION|        P<0.001 **       (e)              (e)              P=0.515          P=0.055                          | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P=0.500          P=0.050                          | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 31      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular                                                                                                               | 
|     Mineralization                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        10/15 (67%)      0/15 (0%)        0/15 (0%)        5/15 (33%)       1/15 (7%)                        | 
|POLY-3 RATE (b)    |        10/13.95         0/14.74          0/13.80          5/14.37          1/11.42                          | 
|POLY-3 PERCENT (g) |        71.7%            0.0%             0.0%             34.8%            8.8%                             | 
|TERMINAL (d)       |        10/13 (77%)      0/14 (0%)        0/13 (0%)        5/14 (36%)       1/7 (14%)                        | 
|FIRST INCIDENCE    |        280 (T)          ---              ---              280 (T)          280 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.120N         P<0.001N**       P<0.001N**       P=0.042N*        P=0.015N*                        | 
|POLY 3             |        P=0.028N*        P<0.001N**       P<0.001N**       P=0.047N*        P<0.001N**                       | 
|POLY 1.5           |        P=0.020N*        P<0.001N**       P<0.001N**       P=0.054N         P<0.001N**                       | 
|POLY 6             |        P=0.040N*        P<0.001N**       P<0.001N**       P=0.040N*        P<0.001N**                       | 
|LOGISTIC REGRESSION|        P=0.120N         (e)              (e)              P=0.042N*        P=0.015N*                        | 
|COCH-ARM / FISHERS |        P=0.036N*        P<0.001N**       P<0.001N**       P=0.072N         P<0.001N**                       | 
|ORDER RESTRICTED   |        P<0.001N**       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular                                                                                                               | 
|     Mineralization                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/15 (27%)       0/15 (0%)        0/15 (0%)        0/15 (0%)        2/15 (13%)                       | 
|POLY-3 RATE (b)    |        4/13.88          0/14.62          0/14.15          0/14.62          2/12.41                          | 
|POLY-3 PERCENT (g) |        28.8%            0.0%             0.0%             0.0%             16.1%                            | 
|TERMINAL (d)       |        4/13 (31%)       0/14 (0%)        0/12 (0%)        0/14 (0%)        2/9 (22%)                        | 
|FIRST INCIDENCE    |        281 (T)          ---              ---              ---              281 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.625N         P=0.047N*        P=0.064N         P=0.047N*        P=0.517N                         | 
|POLY 3             |        P=0.496N         P=0.038N*        P=0.042N*        P=0.038N*        P=0.381N                         | 
|POLY 1.5           |        P=0.505N         P=0.039N*        P=0.041N*        P=0.039N*        P=0.354N                         | 
|POLY 6             |        P=0.483N         P=0.039N*        P=0.044N*        P=0.039N*        P=0.411N                         | 
|LOGISTIC REGRESSION|        P=0.625N         (e)              (e)              (e)              P=0.517N                         | 
|COCH-ARM / FISHERS |        P=0.500N         P=0.050N         P=0.050N         P=0.050N         P=0.326N                         | 
|ORDER RESTRICTED   |        P=0.013N*        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 32      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular: Muscularis                                                                                                   | 
|     Mineralization                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        1/15 (7%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        0/13.95          0/14.74          0/13.80          1/14.37          0/11.42                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             7.0%             0.0%                             | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/13 (0%)        1/14 (7%)        0/7 (0%)                         | 
|FIRST INCIDENCE    |        ---              ---              ---              280 (T)          ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.580          (e)              (e)              P=0.515          (e)                              | 
|POLY 3             |        P=0.512          (e)              (e)              P=0.506          (e)                              | 
|POLY 1.5           |        P=0.570          (e)              (e)              P=0.503          (e)                              | 
|POLY 6             |        P=0.431          (e)              (e)              P=0.509          (e)                              | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.515          (e)                              | 
|COCH-ARM / FISHERS |        P=0.639          (e)              (e)              P=0.500          (e)                              | 
|ORDER RESTRICTED   |        P=0.387          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Glandular: Muscularis                                                                                                   | 
|     Mineralization                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        2/15 (13%)                       | 
|POLY-3 RATE (b)    |        0/13.88          0/14.62          0/14.15          0/14.62          2/12.41                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             16.1%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/12 (0%)        0/14 (0%)        2/9 (22%)                        | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              281 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.009 **       (e)              (e)              (e)              P=0.157                          | 
|POLY 3             |        P=0.017 *        (e)              (e)              (e)              P=0.205                          | 
|POLY 1.5           |        P=0.017 *        (e)              (e)              (e)              P=0.217                          | 
|POLY 6             |        P=0.016 *        (e)              (e)              (e)              P=0.193                          | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              P=0.157                          | 
|COCH-ARM / FISHERS |        P=0.021 *        (e)              (e)              (e)              P=0.241                          | 
|ORDER RESTRICTED   |        P=0.010 *        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 33      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/15 (13%)       0/15 (0%)        1/15 (7%)        0/15 (0%)        4/15 (27%)                       | 
|POLY-3 RATE (b)    |        2/15.00          0/14.74          1/14.66          0/14.37          4/12.77                          | 
|POLY-3 PERCENT (g) |        13.3%            0.0%             6.8%             0.0%             31.3%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/14 (0%)        0/13 (0%)        0/14 (0%)        0/7 (0%)                         | 
|FIRST INCIDENCE    |        196              ---              146              ---              210                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.039 *        P=0.232N         P=0.508N         P=0.240N         P=0.231                          | 
|POLY 3             |        P=0.048 *        P=0.236N         P=0.508N         P=0.241N         P=0.249                          | 
|POLY 1.5           |        P=0.051          P=0.234N         P=0.504N         P=0.238N         P=0.280                          | 
|POLY 6             |        P=0.046 *        P=0.239N         P=0.514N         P=0.245N         P=0.217                          | 
|LOGISTIC REGRESSION|        P=0.367          (e)              (e)              P=0.207N         P=0.662                          | 
|COCH-ARM / FISHERS |        P=0.061          P=0.241N         P=0.500N         P=0.241N         P=0.326                          | 
|ORDER RESTRICTED   |        P=0.013 *        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        2/15 (13%)       0/15 (0%)        1/15 (7%)        3/15 (20%)                       | 
|POLY-3 RATE (b)    |        0/13.88          2/15.00          0/14.15          1/14.62          3/14.05                          | 
|POLY-3 PERCENT (g) |        0.0%             13.3%            0.0%             6.8%             21.4%                            | 
|TERMINAL (d)       |        0/13 (0%)        1/14 (7%)        0/12 (0%)        1/14 (7%)        0/9 (0%)                         | 
|FIRST INCIDENCE    |        ---              239              ---              281 (T)          186                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.047 *        P=0.256          (e)              P=0.515          P=0.111                          | 
|POLY 3             |        P=0.066          P=0.250          (e)              P=0.510          P=0.107                          | 
|POLY 1.5           |        P=0.066          P=0.246          (e)              P=0.510          P=0.108                          | 
|POLY 6             |        P=0.067          P=0.252          (e)              P=0.509          P=0.107                          | 
|LOGISTIC REGRESSION|        P=0.105          P=0.197          (e)              P=0.515          P=0.108                          | 
|COCH-ARM / FISHERS |        P=0.066          P=0.241          (e)              P=0.500          P=0.112                          | 
|ORDER RESTRICTED   |        P=0.028 *        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/14/04                           EXPERIMENT: 99035 TEST: 01                                            Page 34      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
GLY                                                                                                                                 
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus: Endometrium                                                                                                              | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                                                                                                             | 
|POLY-3 RATE (b)    |                                                                                                             | 
|POLY-3 PERCENT (g) |                                                                                                             | 
|TERMINAL (d)       |                                                                                                             | 
|FIRST INCIDENCE    |                                                                                                             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                                                                                                             | 
|POLY 3             |                                                                                                             | 
|POLY 1.5           |                                                                                                             | 
|POLY 6             |                                                                                                             | 
|LOGISTIC REGRESSION|                                                                                                             | 
|COCH-ARM / FISHERS |                                                                                                             | 
|ORDER RESTRICTED   |                                                                                                             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus: Endometrium                                                                                                              | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        13/15 (87%)      14/15 (93%)      10/15 (67%)      14/15 (93%)      9/15 (60%)                       | 
|POLY-3 RATE (b)    |        13/13.88         14/14.62         10/14.15         14/15.00         9/12.44                          | 
|POLY-3 PERCENT (g) |        93.6%            95.8%            70.7%            93.3%            72.3%                            | 
|TERMINAL (d)       |        13/13 (100%)     14/14 (100%)     10/12 (83%)      13/14 (93%)      8/9 (89%)                        | 
|FIRST INCIDENCE    |        281 (T)          281 (T)          281 (T)          239              278                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.561          P=1.000          P=0.217N         P=0.760          P=0.740N                         | 
|POLY 3             |        P=0.109N         P=0.741          P=0.121N         P=0.765N         P=0.146N                         | 
|POLY 1.5           |        P=0.072N         P=0.702          P=0.121N         P=0.731          P=0.102N                         | 
|POLY 6             |        P=0.155N         P=0.767          P=0.138N         P=0.742N         P=0.221N                         | 
|LOGISTIC REGRESSION|        P=0.259N         P=1.000          P=0.217N         P=0.716          (e)                              | 
|COCH-ARM / FISHERS |        P=0.051N         P=0.500          P=0.195N         P=0.500          P=0.107N                         | 
|ORDER RESTRICTED   |        P=0.060N         (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
(a)  Number of tumor-bearing animals /  number of animals examined at site.                                                         
                                                                                                                                   
(b)  Number of tumor-bearing animals / Poly-3 number                                                                                
(d)  Observed incidence at terminal kill.                                                                                           
(f)  Beneath the control incidence are the P-values associated with the trend                                                       
test.  Beneath the dosed group incidence are the P-values corresponding to                                                          
pairwise comparisons between the controls and that dosed group.  The life                                                           
table analysis regards tumors in animals dying prior to  terminal kill as                                                           
 being (directly or indirectly) the cause of death.                                                                                 
Logistic regression is an alternative                                                                                               
 method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage                                                       
and Fishers exact tests compare directly the overall incidence rates                                                                
For all tests a negative trend is indicated by N                                                                                    
(e)  Value of Statistic cannot be computed.                                                                                         
(g)  Poly-3 adjusted lifetime tumor incidence.                                                                                      
(I)  Interim sacrifice                                                                                                              
(T)  Terminal sacrifice                                                                                                             
#   Tumor rates based on number of animals necropsied.                                                                              
*   To the right of any statistical result, indicates significance at (P<=0.05).                                                    
**  To the right of any statistical result, indicates significance at (P<=0.01).