National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/17427

TDMS Study 99034-01 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                          TRANSGENIC MODEL EVALUATION II (BENZENE)                       DATE: 11/05/03       
EXPERIMENT: 99034 TEST: 01                                                                                     TIME: 14:55:50       
TEST TYPE:  SUBCHRON 26-WEEK                    CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-65406                              ROUTE: GAVAGE                                                  NTP C#: C99034       
PATHOLOGIST: MISSING                                                                                           CAS: 71-43-2         
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                           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 (BENZENE)                       DATE: 11/05/03       
EXPERIMENT: 99034 TEST: 01                                                                                     TIME: 14:55:50       
TEST TYPE:  SUBCHRON 26-WEEK                    CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-65406                              ROUTE: GAVAGE                                                  NTP C#: C99034       
PATHOLOGIST: MISSING                                                                                           CAS: 71-43-2         
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF        TRANSGENIC MODEL EVALUATION II (BEN                                                                       
===============================================================                                                                     
Male Mice                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Bone Marrow                            Atrophy                                                                                      
                                       Pigmentation Hemosiderin                                                                     
Kidney                                 Nephropathy                                                                                  
Lung                                   Inflammation Chronic                                                                         
Lymph Node, Mandibular                 Atrophy                                                                                      
Lymph Node, Mesenteric                 Atrophy                                                                                      
Lymph Node: Mediastinal                Atrophy                                                                                      
Skin                                   Pigmentation                                                                                 
Spleen                                 Hematopoietic Cell Proliferation                                                             
Spleen: Lymphoid Follicle              Atrophy                                                                                      
Stomach, Forestomach                   Hyperplasia                                                                                  
Thymus                                 Atrophy                                                                                      
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Liver                                  Inflammation Chronic                                                                         
Lung: Alveolar Epithelium              Hyperplasia Focal                                                                            
Lymph Node, Mesenteric                 Atrophy                                                                                      
Lymph Node: Mediastinal                Atrophy                                                                                      
Mammary Gland                          Hyperplasia                                                                                  
Skin                                   Pigmentation                                                                                 
Uterus: Endometrium                    Hyperplasia Cystic                                                                           
===============================================================                                                                     
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions in        Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II 
(BEN                                                                                                                                
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone Marrow                                                                                                                      | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        10/15 (67%)      12/15 (80%)                      | 
|POLY-3 RATE (b)    |        0/15.00          0/15.00          0/15.00          10/15.00         12/14.00                         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             66.7%            85.7%                            | 
|TERMINAL (d)       |        0/15 (0%)        0/15 (0%)        0/15 (0%)        10/15 (67%)      12/14 (86%)                      | 
|FIRST INCIDENCE    |        ---              ---              ---              188 (T)          188 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 3             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 6             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|LOGISTIC REGRESSION|        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|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                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone Marrow                                                                                                                      | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        0/15.00          0/15.00          0/15.00          0/15.00          0/15.00                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%                             | 
|TERMINAL (d)       |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (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:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 2       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone Marrow                                                                                                                      | 
|     Pigmentation Hemosiderin                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        13/15 (87%)      13/15 (87%)      15/15 (100%)     14/15 (93%)                      | 
|POLY-3 RATE (b)    |        1/15.00          13/15.00         13/15.00         15/15.00         14/14.00                         | 
|POLY-3 PERCENT (g) |        6.7%             86.7%            86.7%            100.0%           100.0%                           | 
|TERMINAL (d)       |        1/15 (7%)        13/15 (87%)      13/15 (87%)      15/15 (100%)     14/14 (100%)                     | 
|FIRST INCIDENCE    |        188 (T)          188 (T)          188 (T)          188 (T)          188 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **                       | 
|POLY 3             |        P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **                       | 
|POLY 1.5           |        P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **                       | 
|POLY 6             |        P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **                       | 
|LOGISTIC REGRESSION|        P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **                       | 
|COCH-ARM / FISHERS |        P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **                       | 
|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                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone Marrow                                                                                                                      | 
|     Pigmentation Hemosiderin                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        0/15.00          0/15.00          0/15.00          0/15.00          0/15.00                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%                             | 
|TERMINAL (d)       |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (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:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 3       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Small, Duodenum                                                                                                        | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        0/15.00          0/15.00          0/15.00          0/15.00          0/14.00                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%                             | 
|TERMINAL (d)       |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/14 (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                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Intestine Small, Duodenum                                                                                                        | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        2/15 (13%)       0/15 (0%)                        | 
|POLY-3 RATE (b)    |        0/15.00          0/15.00          0/15.00          2/15.00          0/15.00                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             13.3%            0.0%                             | 
|TERMINAL (d)       |        0/15 (0%)        0/15 (0%)        0/15 (0%)        2/15 (13%)       0/15 (0%)                        | 
|FIRST INCIDENCE    |        ---              ---              ---              189 (T)          ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.500          (e)              (e)              P=0.236          (e)                              | 
|POLY 3             |        P=0.500          (e)              (e)              P=0.232          (e)                              | 
|POLY 1.5           |        P=0.500          (e)              (e)              P=0.232          (e)                              | 
|POLY 6             |        P=0.500          (e)              (e)              P=0.232          (e)                              | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.236          (e)                              | 
|COCH-ARM / FISHERS |        P=0.500          (e)              (e)              P=0.241          (e)                              | 
|ORDER RESTRICTED   |        P=0.205          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 4       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Casts Protein                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        0/15 (0%)        2/15 (13%)       1/15 (7%)        2/15 (13%)                       | 
|POLY-3 RATE (b)    |        1/15.00          0/15.00          2/15.00          1/15.00          2/14.00                          | 
|POLY-3 PERCENT (g) |        6.7%             0.0%             13.3%            6.7%             14.3%                            | 
|TERMINAL (d)       |        1/15 (7%)        0/15 (0%)        2/15 (13%)       1/15 (7%)        2/14 (14%)                       | 
|FIRST INCIDENCE    |        188 (T)          ---              188 (T)          188 (T)          188 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.252          P=0.500N         P=0.500          P=0.764          P=0.475                          | 
|POLY 3             |        P=0.254          P=0.500N         P=0.500          P=0.760          P=0.476                          | 
|POLY 1.5           |        P=0.254          P=0.500N         P=0.500          P=0.760          P=0.476                          | 
|POLY 6             |        P=0.254          P=0.500N         P=0.500          P=0.760          P=0.476                          | 
|LOGISTIC REGRESSION|        P=0.252          (e)              P=0.500          P=0.764          P=0.475                          | 
|COCH-ARM / FISHERS |        P=0.274          P=0.500N         P=0.500          P=0.759N         P=0.500                          | 
|ORDER RESTRICTED   |        P=0.250          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Casts Protein                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/15 (33%)       4/15 (27%)       5/15 (33%)       8/15 (53%)       7/15 (47%)                       | 
|POLY-3 RATE (b)    |        5/15.00          4/15.00          5/15.00          8/15.00          7/15.00                          | 
|POLY-3 PERCENT (g) |        33.3%            26.7%            33.3%            53.3%            46.7%                            | 
|TERMINAL (d)       |        5/15 (33%)       4/15 (27%)       5/15 (33%)       8/15 (53%)       7/15 (47%)                       | 
|FIRST INCIDENCE    |        189 (T)          189 (T)          189 (T)          189 (T)          189 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.140          P=0.500N         P=0.648          P=0.234          P=0.357                          | 
|POLY 3             |        P=0.141          P=0.500N         P=0.646          P=0.234          P=0.358                          | 
|POLY 1.5           |        P=0.141          P=0.500N         P=0.646          P=0.234          P=0.358                          | 
|POLY 6             |        P=0.141          P=0.500N         P=0.646          P=0.234          P=0.358                          | 
|LOGISTIC REGRESSION|        P=0.140          P=0.500N         P=0.648          P=0.234          P=0.357                          | 
|COCH-ARM / FISHERS |        P=0.138          P=0.500N         P=0.650N         P=0.231          P=0.355                          | 
|ORDER RESTRICTED   |        P=0.225          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 5       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        1/15 (7%)        0/15 (0%)        2/15 (13%)       4/15 (27%)                       | 
|POLY-3 RATE (b)    |        1/15.00          1/15.00          0/15.00          2/15.00          4/14.00                          | 
|POLY-3 PERCENT (g) |        6.7%             6.7%             0.0%             13.3%            28.6%                            | 
|TERMINAL (d)       |        1/15 (7%)        1/15 (7%)        0/15 (0%)        2/15 (13%)       4/14 (29%)                       | 
|FIRST INCIDENCE    |        188 (T)          188 (T)          ---              188 (T)          188 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.019 *        P=0.764          P=0.500N         P=0.500          P=0.147                          | 
|POLY 3             |        P=0.019 *        P=0.760          P=0.500N         P=0.500          P=0.141                          | 
|POLY 1.5           |        P=0.019 *        P=0.760          P=0.500N         P=0.500          P=0.141                          | 
|POLY 6             |        P=0.019 *        P=0.760          P=0.500N         P=0.500          P=0.141                          | 
|LOGISTIC REGRESSION|        P=0.019 *        P=0.764          (e)              P=0.500          P=0.143                          | 
|COCH-ARM / FISHERS |        P=0.024 *        P=0.759N         P=0.500N         P=0.500          P=0.165                          | 
|ORDER RESTRICTED   |        P=0.024 *        (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)        |        3/15 (20%)       0/15 (0%)        1/15 (7%)        2/15 (13%)       1/15 (7%)                        | 
|POLY-3 RATE (b)    |        3/15.00          0/15.00          1/15.00          2/15.00          1/15.00                          | 
|POLY-3 PERCENT (g) |        20.0%            0.0%             6.7%             13.3%            6.7%                             | 
|TERMINAL (d)       |        3/15 (20%)       0/15 (0%)        1/15 (7%)        2/15 (13%)       1/15 (7%)                        | 
|FIRST INCIDENCE    |        189 (T)          ---              189 (T)          189 (T)          189 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.445N         P=0.116N         P=0.299N         P=0.500N         P=0.299N                         | 
|POLY 3             |        P=0.445N         P=0.106N         P=0.298N         P=0.500N         P=0.298N                         | 
|POLY 1.5           |        P=0.445N         P=0.106N         P=0.298N         P=0.500N         P=0.298N                         | 
|POLY 6             |        P=0.445N         P=0.106N         P=0.298N         P=0.500N         P=0.298N                         | 
|LOGISTIC REGRESSION|        P=0.445N         (e)              P=0.299N         P=0.500N         P=0.299N                         | 
|COCH-ARM / FISHERS |        P=0.444N         P=0.112N         P=0.299N         P=0.500N         P=0.299N                         | 
|ORDER RESTRICTED   |        P=0.175N         (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 6       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 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)        |        3/15 (20%)       6/15 (40%)       1/15 (7%)        3/15 (20%)       1/15 (7%)                        | 
|POLY-3 RATE (b)    |        3/15.00          6/15.00          1/15.00          3/15.00          1/14.00                          | 
|POLY-3 PERCENT (g) |        20.0%            40.0%            6.7%             20.0%            7.1%                             | 
|TERMINAL (d)       |        3/15 (20%)       6/15 (40%)       1/15 (7%)        3/15 (20%)       1/14 (7%)                        | 
|FIRST INCIDENCE    |        188 (T)          188 (T)          188 (T)          188 (T)          188 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.121N         P=0.217          P=0.299N         P=0.673          P=0.324N                         | 
|POLY 3             |        P=0.118N         P=0.215          P=0.298N         P=0.670          P=0.324N                         | 
|POLY 1.5           |        P=0.118N         P=0.215          P=0.298N         P=0.670          P=0.324N                         | 
|POLY 6             |        P=0.118N         P=0.215          P=0.298N         P=0.670          P=0.324N                         | 
|LOGISTIC REGRESSION|        P=0.121N         P=0.217          P=0.299N         P=0.673          P=0.324N                         | 
|COCH-ARM / FISHERS |        P=0.104N         P=0.213          P=0.299N         P=0.674N         P=0.299N                         | 
|ORDER RESTRICTED   |        P=0.088N         (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)        |        10/15 (67%)      6/15 (40%)       6/15 (40%)       4/15 (27%)       11/15 (73%)                      | 
|POLY-3 RATE (b)    |        10/15.00         6/15.00          6/15.00          4/15.00          11/15.00                         | 
|POLY-3 PERCENT (g) |        66.7%            40.0%            40.0%            26.7%            73.3%                            | 
|TERMINAL (d)       |        10/15 (67%)      6/15 (40%)       6/15 (40%)       4/15 (27%)       11/15 (73%)                      | 
|FIRST INCIDENCE    |        189 (T)          189 (T)          189 (T)          189 (T)          189 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.233          P=0.140N         P=0.140N         P=0.036N*        P=0.500                          | 
|POLY 3             |        P=0.224          P=0.136N         P=0.136N         P=0.027N*        P=0.500                          | 
|POLY 1.5           |        P=0.224          P=0.136N         P=0.136N         P=0.027N*        P=0.500                          | 
|POLY 6             |        P=0.224          P=0.136N         P=0.136N         P=0.027N*        P=0.500                          | 
|LOGISTIC REGRESSION|        P=0.233          P=0.140N         P=0.140N         P=0.036N*        P=0.500                          | 
|COCH-ARM / FISHERS |        P=0.231          P=0.136N         P=0.136N         P=0.033N*        P=0.500                          | 
|ORDER RESTRICTED   |        P=0.066          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 7       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/15 (13%)       0/15 (0%)        1/15 (7%)        3/15 (20%)       5/15 (33%)                       | 
|POLY-3 RATE (b)    |        2/15.00          0/15.00          1/15.00          3/15.00          5/14.00                          | 
|POLY-3 PERCENT (g) |        13.3%            0.0%             6.7%             20.0%            35.7%                            | 
|TERMINAL (d)       |        2/15 (13%)       0/15 (0%)        1/15 (7%)        3/15 (20%)       5/14 (36%)                       | 
|FIRST INCIDENCE    |        188 (T)          ---              188 (T)          188 (T)          188 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.011 *        P=0.236N         P=0.500N         P=0.500          P=0.169                          | 
|POLY 3             |        P=0.010 *        P=0.232N         P=0.500N         P=0.500          P=0.166                          | 
|POLY 1.5           |        P=0.010 *        P=0.232N         P=0.500N         P=0.500          P=0.166                          | 
|POLY 6             |        P=0.010 *        P=0.232N         P=0.500N         P=0.500          P=0.166                          | 
|LOGISTIC REGRESSION|        P=0.011 *        (e)              P=0.500N         P=0.500          P=0.169                          | 
|COCH-ARM / FISHERS |        P=0.014 *        P=0.241N         P=0.500N         P=0.500          P=0.195                          | 
|ORDER RESTRICTED   |        P=0.018 *        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/15 (13%)       2/15 (13%)       0/15 (0%)        0/15 (0%)        2/15 (13%)                       | 
|POLY-3 RATE (b)    |        2/15.00          2/15.00          0/15.00          0/15.00          2/15.00                          | 
|POLY-3 PERCENT (g) |        13.3%            13.3%            0.0%             0.0%             13.3%                            | 
|TERMINAL (d)       |        2/15 (13%)       2/15 (13%)       0/15 (0%)        0/15 (0%)        2/15 (13%)                       | 
|FIRST INCIDENCE    |        189 (T)          189 (T)          ---              ---              189 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.618          P=0.701          P=0.236N         P=0.236N         P=0.701                          | 
|POLY 3             |        P=0.618          P=0.698          P=0.232N         P=0.232N         P=0.698                          | 
|POLY 1.5           |        P=0.618          P=0.698          P=0.232N         P=0.232N         P=0.698                          | 
|POLY 6             |        P=0.618          P=0.698          P=0.232N         P=0.232N         P=0.698                          | 
|LOGISTIC REGRESSION|        P=0.618          P=0.701          (e)              (e)              P=0.701                          | 
|COCH-ARM / FISHERS |        P=0.618          P=0.701N         P=0.241N         P=0.241N         P=0.701N                         | 
|ORDER RESTRICTED   |        P=0.322N         (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 8       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 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%)        0/15 (0%)        1/15 (7%)        0/15 (0%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        0/15.00          0/15.00          1/15.00          0/15.00          0/14.00                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             6.7%             0.0%             0.0%                             | 
|TERMINAL (d)       |        0/15 (0%)        0/15 (0%)        1/15 (7%)        0/15 (0%)        0/14 (0%)                        | 
|FIRST INCIDENCE    |        ---              ---              188 (T)          ---              ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.649N         (e)              P=0.500          (e)              (e)                              | 
|POLY 3             |        P=0.639N         (e)              P=0.500          (e)              (e)                              | 
|POLY 1.5           |        P=0.639N         (e)              P=0.500          (e)              (e)                              | 
|POLY 6             |        P=0.639N         (e)              P=0.500          (e)              (e)                              | 
|LOGISTIC REGRESSION|        (e)              (e)              P=0.500          (e)              (e)                              | 
|COCH-ARM / FISHERS |        P=0.639N         (e)              P=0.500          (e)              (e)                              | 
|ORDER RESTRICTED   |        P=0.522          (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%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        3/15 (20%)                       | 
|POLY-3 RATE (b)    |        1/15.00          0/15.00          0/15.00          0/15.00          3/15.00                          | 
|POLY-3 PERCENT (g) |        6.7%             0.0%             0.0%             0.0%             20.0%                            | 
|TERMINAL (d)       |        1/15 (7%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        3/15 (20%)                       | 
|FIRST INCIDENCE    |        189 (T)          ---              ---              ---              189 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.036 *        P=0.500N         P=0.500N         P=0.500N         P=0.299                          | 
|POLY 3             |        P=0.031 *        P=0.500N         P=0.500N         P=0.500N         P=0.298                          | 
|POLY 1.5           |        P=0.031 *        P=0.500N         P=0.500N         P=0.500N         P=0.298                          | 
|POLY 6             |        P=0.031 *        P=0.500N         P=0.500N         P=0.500N         P=0.298                          | 
|LOGISTIC REGRESSION|        P=0.036 *        (e)              (e)              (e)              P=0.299                          | 
|COCH-ARM / FISHERS |        P=0.035 *        P=0.500N         P=0.500N         P=0.500N         P=0.299                          | 
|ORDER RESTRICTED   |        P=0.014 *        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 9       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        6/14 (43%)       11/14 (79%)                      | 
|POLY-3 RATE (b)    |        0/15.00          0/15.00          0/15.00          6/14.00          11/13.00                         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             42.9%            84.6%                            | 
|TERMINAL (d)       |        0/15 (0%)        0/15 (0%)        0/15 (0%)        6/14 (43%)       11/13 (85%)                      | 
|FIRST INCIDENCE    |        ---              ---              ---              188 (T)          188 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.009 **       P<0.001 **                       | 
|POLY 3             |        P<0.001 **       (e)              (e)              P=0.003 **       P<0.001 **                       | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P=0.003 **       P<0.001 **                       | 
|POLY 6             |        P<0.001 **       (e)              (e)              P=0.003 **       P<0.001 **                       | 
|LOGISTIC REGRESSION|        P<0.001 **       (e)              (e)              P=0.009 **       P<0.001 **                       | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P=0.006 **       P<0.001 **                       | 
|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                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/14 (0%)        1/15 (7%)        2/15 (13%)       4/15 (27%)       0/15 (0%)                        | 
|POLY-3 RATE (b)    |        0/14.00          1/15.00          2/15.00          4/15.00          0/15.00                          | 
|POLY-3 PERCENT (g) |        0.0%             6.7%             13.3%            26.7%            0.0%                             | 
|TERMINAL (d)       |        0/14 (0%)        1/15 (7%)        2/15 (13%)       4/15 (27%)       0/15 (0%)                        | 
|FIRST INCIDENCE    |        ---              189 (T)          189 (T)          189 (T)          ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.595N         P=0.514          P=0.251          P=0.065          (e)                              | 
|POLY 3             |        P=0.598N         P=0.514          P=0.247          P=0.053          (e)                              | 
|POLY 1.5           |        P=0.598N         P=0.514          P=0.247          P=0.053          (e)                              | 
|POLY 6             |        P=0.598N         P=0.514          P=0.247          P=0.053          (e)                              | 
|LOGISTIC REGRESSION|        (e)              P=0.514          P=0.251          P=0.065          (e)                              | 
|COCH-ARM / FISHERS |        P=0.595N         P=0.517          P=0.259          P=0.057          (e)                              | 
|ORDER RESTRICTED   |        P=0.176          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 10      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 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)        |        2/15 (13%)       1/15 (7%)        1/15 (7%)        0/14 (0%)        0/14 (0%)                        | 
|POLY-3 RATE (b)    |        2/15.00          1/15.00          1/15.00          0/14.00          0/13.00                          | 
|POLY-3 PERCENT (g) |        13.3%            6.7%             6.7%             0.0%             0.0%                             | 
|TERMINAL (d)       |        2/15 (13%)       1/15 (7%)        1/15 (7%)        0/14 (0%)        0/13 (0%)                        | 
|FIRST INCIDENCE    |        188 (T)          188 (T)          188 (T)          ---              ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.118N         P=0.500N         P=0.500N         P=0.251N         P=0.268N                         | 
|POLY 3             |        P=0.115N         P=0.500N         P=0.500N         P=0.247N         P=0.265N                         | 
|POLY 1.5           |        P=0.115N         P=0.500N         P=0.500N         P=0.247N         P=0.265N                         | 
|POLY 6             |        P=0.115N         P=0.500N         P=0.500N         P=0.247N         P=0.265N                         | 
|LOGISTIC REGRESSION|        P=0.118N         P=0.500N         P=0.500N         (e)              (e)                              | 
|COCH-ARM / FISHERS |        P=0.110N         P=0.500N         P=0.500N         P=0.259N         P=0.259N                         | 
|ORDER RESTRICTED   |        P=0.107N         (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)        |        1/14 (7%)        4/15 (27%)       2/15 (13%)       5/15 (33%)       3/15 (20%)                       | 
|POLY-3 RATE (b)    |        1/14.00          4/15.00          2/15.00          5/15.00          3/15.00                          | 
|POLY-3 PERCENT (g) |        7.1%             26.7%            13.3%            33.3%            20.0%                            | 
|TERMINAL (d)       |        1/14 (7%)        4/15 (27%)       2/15 (13%)       5/15 (33%)       3/15 (20%)                       | 
|FIRST INCIDENCE    |        189 (T)          189 (T)          189 (T)          189 (T)          189 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.328          P=0.189          P=0.525          P=0.104          P=0.324                          | 
|POLY 3             |        P=0.328          P=0.185          P=0.524          P=0.096          P=0.324                          | 
|POLY 1.5           |        P=0.328          P=0.185          P=0.524          P=0.096          P=0.324                          | 
|POLY 6             |        P=0.328          P=0.185          P=0.524          P=0.096          P=0.324                          | 
|LOGISTIC REGRESSION|        P=0.328          P=0.189          P=0.525          P=0.104          P=0.324                          | 
|COCH-ARM / FISHERS |        P=0.327          P=0.186          P=0.527          P=0.099          P=0.326                          | 
|ORDER RESTRICTED   |        P=0.163          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 11      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Infiltration Cellular Polymorphonuclear                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        1/14 (7%)        1/14 (7%)                        | 
|POLY-3 RATE (b)    |        0/15.00          0/15.00          0/15.00          1/14.00          1/13.00                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             7.1%             7.7%                             | 
|TERMINAL (d)       |        0/15 (0%)        0/15 (0%)        0/15 (0%)        1/14 (7%)        1/13 (8%)                        | 
|FIRST INCIDENCE    |        ---              ---              ---              188 (T)          188 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.133          (e)              (e)              P=0.486          P=0.471                          | 
|POLY 3             |        P=0.130          (e)              (e)              P=0.486          P=0.471                          | 
|POLY 1.5           |        P=0.130          (e)              (e)              P=0.486          P=0.472                          | 
|POLY 6             |        P=0.130          (e)              (e)              P=0.486          P=0.471                          | 
|LOGISTIC REGRESSION|        P=0.131          (e)              (e)              P=0.486          P=0.471                          | 
|COCH-ARM / FISHERS |        P=0.143          (e)              (e)              P=0.483          P=0.483                          | 
|ORDER RESTRICTED   |        P=0.192          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Infiltration Cellular Polymorphonuclear                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/14 (7%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        2/15 (13%)                       | 
|POLY-3 RATE (b)    |        1/14.00          0/15.00          0/15.00          0/15.00          2/15.00                          | 
|POLY-3 PERCENT (g) |        7.1%             0.0%             0.0%             0.0%             13.3%                            | 
|TERMINAL (d)       |        1/14 (7%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        2/15 (13%)                       | 
|FIRST INCIDENCE    |        189 (T)          ---              ---              ---              189 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.156          P=0.486N         P=0.486N         P=0.486N         P=0.525                          | 
|POLY 3             |        P=0.153          P=0.486N         P=0.486N         P=0.486N         P=0.524                          | 
|POLY 1.5           |        P=0.153          P=0.486N         P=0.486N         P=0.486N         P=0.524                          | 
|POLY 6             |        P=0.153          P=0.486N         P=0.486N         P=0.486N         P=0.524                          | 
|LOGISTIC REGRESSION|        P=0.156          (e)              (e)              (e)              P=0.525                          | 
|COCH-ARM / FISHERS |        P=0.154          P=0.483N         P=0.483N         P=0.483N         P=0.527                          | 
|ORDER RESTRICTED   |        P=0.088          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 12      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        2/15 (13%)       2/14 (14%)       13/15 (87%)      13/15 (87%)                      | 
|POLY-3 RATE (b)    |        1/15.00          2/15.00          2/14.00          13/15.00         13/14.00                         | 
|POLY-3 PERCENT (g) |        6.7%             13.3%            14.3%            86.7%            92.9%                            | 
|TERMINAL (d)       |        1/15 (7%)        2/15 (13%)       2/14 (14%)       13/15 (87%)      13/14 (93%)                      | 
|FIRST INCIDENCE    |        188 (T)          188 (T)          188 (T)          188 (T)          188 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.500          P=0.475          P<0.001 **       P<0.001 **                       | 
|POLY 3             |        P<0.001 **       P=0.500          P=0.476          P<0.001 **       P<0.001 **                       | 
|POLY 1.5           |        P<0.001 **       P=0.500          P=0.476          P<0.001 **       P<0.001 **                       | 
|POLY 6             |        P<0.001 **       P=0.500          P=0.476          P<0.001 **       P<0.001 **                       | 
|LOGISTIC REGRESSION|        P<0.001 **       P=0.500          P=0.475          P<0.001 **       P<0.001 **                       | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.500          P=0.473          P<0.001 **       P<0.001 **                       | 
|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                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        2/15 (13%)       3/15 (20%)       8/15 (53%)       6/15 (40%)                       | 
|POLY-3 RATE (b)    |        0/15.00          2/15.00          3/15.00          8/15.00          6/15.00                          | 
|POLY-3 PERCENT (g) |        0.0%             13.3%            20.0%            53.3%            40.0%                            | 
|TERMINAL (d)       |        0/15 (0%)        2/15 (13%)       3/15 (20%)       8/15 (53%)       6/15 (40%)                       | 
|FIRST INCIDENCE    |        ---              189 (T)          189 (T)          189 (T)          189 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.003 **       P=0.236          P=0.116          P=0.002 **       P=0.012 *                        | 
|POLY 3             |        P=0.002 **       P=0.232          P=0.106          P<0.001 **       P=0.005 **                       | 
|POLY 1.5           |        P=0.002 **       P=0.232          P=0.106          P<0.001 **       P=0.005 **                       | 
|POLY 6             |        P=0.002 **       P=0.232          P=0.106          P<0.001 **       P=0.005 **                       | 
|LOGISTIC REGRESSION|        (e)              P=0.236          P=0.116          P=0.002 **       P=0.012 *                        | 
|COCH-ARM / FISHERS |        P=0.003 **       P=0.241          P=0.112          P<0.001 **       P=0.008 **                       | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 13      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node: Mediastinal                                                                                                          | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/11 (0%)        0/11 (0%)        2/12 (17%)       6/9 (67%)        6/7 (86%)                        | 
|POLY-3 RATE (b)    |        0/11.00          0/11.00          2/12.00          6/9.00           6/7.00                           | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             16.7%            66.7%            85.7%                            | 
|TERMINAL (d)       |        0/11 (0%)        0/11 (0%)        2/12 (17%)       6/9 (67%)        6/7 (86%)                        | 
|FIRST INCIDENCE    |        ---              ---              188 (T)          188 (T)          188 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              P=0.254          P=0.004 **       P<0.001 **                       | 
|POLY 3             |        P<0.001 **       (e)              P=0.249          P<0.001 **       P<0.001 **                       | 
|POLY 1.5           |        P<0.001 **       (e)              P=0.249          P<0.001 **       P<0.001 **                       | 
|POLY 6             |        P<0.001 **       (e)              P=0.249          P<0.001 **       P<0.001 **                       | 
|LOGISTIC REGRESSION|        (e)              (e)              P=0.254          P=0.004 **       P<0.001 **                       | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              P=0.261          P=0.002 **       P<0.001 **                       | 
|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                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node: Mediastinal                                                                                                          | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/13 (0%)        0/11 (0%)        2/11 (18%)       4/12 (33%)       2/13 (15%)                       | 
|POLY-3 RATE (b)    |        0/13.00          0/11.00          2/11.00          4/12.00          2/13.00                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             18.2%            33.3%            15.4%                            | 
|TERMINAL (d)       |        0/13 (0%)        0/11 (0%)        2/11 (18%)       4/12 (33%)       2/13 (15%)                       | 
|FIRST INCIDENCE    |        ---              ---              189 (T)          189 (T)          189 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.114          (e)              P=0.199          P=0.045 *        P=0.235                          | 
|POLY 3             |        P=0.105          (e)              P=0.190          P=0.032 *        P=0.230                          | 
|POLY 1.5           |        P=0.105          (e)              P=0.190          P=0.032 *        P=0.230                          | 
|POLY 6             |        P=0.105          (e)              P=0.190          P=0.032 *        P=0.230                          | 
|LOGISTIC REGRESSION|        (e)              (e)              P=0.199          P=0.045 *        P=0.235                          | 
|COCH-ARM / FISHERS |        P=0.112          (e)              P=0.199          P=0.039 *        P=0.240                          | 
|ORDER RESTRICTED   |        P=0.039 *        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 14      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/0 (0%)         0/1 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)                         | 
|POLY-3 RATE (b)    |        0/0.00           0/1.00           0/0.00           0/0.00           0/0.00                           | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%                             | 
|TERMINAL (d)       |        0/0 (0%)         0/1 (0%)         0/0 (0%)         0/0 (0%)         0/0 (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                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        2/15 (13%)                       | 
|POLY-3 RATE (b)    |        0/15.00          0/15.00          0/15.00          0/15.00          2/15.00                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             13.3%                            | 
|TERMINAL (d)       |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        2/15 (13%)                       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              189 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.022 *        (e)              (e)              (e)              P=0.236                          | 
|POLY 3             |        P=0.019 *        (e)              (e)              (e)              P=0.232                          | 
|POLY 1.5           |        P=0.019 *        (e)              (e)              (e)              P=0.232                          | 
|POLY 6             |        P=0.019 *        (e)              (e)              (e)              P=0.232                          | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              P=0.236                          | 
|COCH-ARM / FISHERS |        P=0.021 *        (e)              (e)              (e)              P=0.241                          | 
|ORDER RESTRICTED   |        P=0.014 *        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 15      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 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)        |        1/14 (7%)        0/15 (0%)        0/15 (0%)        2/15 (13%)       2/15 (13%)                       | 
|POLY-3 RATE (b)    |        1/14.00          0/15.00          0/15.00          2/15.00          2/15.00                          | 
|POLY-3 PERCENT (g) |        7.1%             0.0%             0.0%             13.3%            13.3%                            | 
|TERMINAL (d)       |        1/14 (7%)        0/15 (0%)        0/15 (0%)        2/15 (13%)       2/15 (13%)                       | 
|FIRST INCIDENCE    |        189 (T)          ---              ---              189 (T)          189 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.134          P=0.486N         P=0.486N         P=0.525          P=0.525                          | 
|POLY 3             |        P=0.134          P=0.486N         P=0.486N         P=0.524          P=0.524                          | 
|POLY 1.5           |        P=0.134          P=0.486N         P=0.486N         P=0.524          P=0.524                          | 
|POLY 6             |        P=0.134          P=0.486N         P=0.486N         P=0.524          P=0.524                          | 
|LOGISTIC REGRESSION|        P=0.134          (e)              (e)              P=0.525          P=0.525                          | 
|COCH-ARM / FISHERS |        P=0.133          P=0.483N         P=0.483N         P=0.527          P=0.527                          | 
|ORDER RESTRICTED   |        P=0.204          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 16      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        15/15 (100%)     15/15 (100%)     15/15 (100%)     14/15 (93%)                      | 
|POLY-3 RATE (b)    |        0/15.00          15/15.00         15/15.00         15/15.00         14/14.00                         | 
|POLY-3 PERCENT (g) |        0.0%             100.0%           100.0%           100.0%           100.0%                           | 
|TERMINAL (d)       |        0/15 (0%)        15/15 (100%)     15/15 (100%)     15/15 (100%)     14/14 (100%)                     | 
|FIRST INCIDENCE    |        ---              188 (T)          188 (T)          188 (T)          188 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **                       | 
|POLY 3             |        P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **                       | 
|POLY 1.5           |        P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **                       | 
|POLY 6             |        P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **                       | 
|LOGISTIC REGRESSION|        (e)              P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **                       | 
|COCH-ARM / FISHERS |        P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **                       | 
|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                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Skin                                                                                                                             | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        1/15 (7%)        8/15 (53%)       15/15 (100%)     15/15 (100%)                     | 
|POLY-3 RATE (b)    |        0/15.00          1/15.00          8/15.00          15/15.00         15/15.00                         | 
|POLY-3 PERCENT (g) |        0.0%             6.7%             53.3%            100.0%           100.0%                           | 
|TERMINAL (d)       |        0/15 (0%)        1/15 (7%)        8/15 (53%)       15/15 (100%)     15/15 (100%)                     | 
|FIRST INCIDENCE    |        ---              189 (T)          189 (T)          189 (T)          189 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.500          P=0.002 **       P<0.001 **       P<0.001 **                       | 
|POLY 3             |        P<0.001 **       P=0.500          P<0.001 **       P<0.001 **       P<0.001 **                       | 
|POLY 1.5           |        P<0.001 **       P=0.500          P<0.001 **       P<0.001 **       P<0.001 **                       | 
|POLY 6             |        P<0.001 **       P=0.500          P<0.001 **       P<0.001 **       P<0.001 **                       | 
|LOGISTIC REGRESSION|        P<0.001 **       P=0.500          P=0.002 **       P<0.001 **       P<0.001 **                       | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.500          P<0.001 **       P<0.001 **       P<0.001 **                       | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 17      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 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)        |        0/15 (0%)        1/15 (7%)        0/15 (0%)        2/15 (13%)       8/15 (53%)                       | 
|POLY-3 RATE (b)    |        0/15.00          1/15.00          0/15.00          2/15.00          8/14.00                          | 
|POLY-3 PERCENT (g) |        0.0%             6.7%             0.0%             13.3%            57.1%                            | 
|TERMINAL (d)       |        0/15 (0%)        1/15 (7%)        0/15 (0%)        2/15 (13%)       8/14 (57%)                       | 
|FIRST INCIDENCE    |        ---              188 (T)          ---              188 (T)          188 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.500          (e)              P=0.236          P<0.001 **                       | 
|POLY 3             |        P<0.001 **       P=0.500          (e)              P=0.232          P<0.001 **                       | 
|POLY 1.5           |        P<0.001 **       P=0.500          (e)              P=0.232          P<0.001 **                       | 
|POLY 6             |        P<0.001 **       P=0.500          (e)              P=0.232          P<0.001 **                       | 
|LOGISTIC REGRESSION|        (e)              P=0.500          (e)              P=0.236          P<0.001 **                       | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.500          (e)              P=0.241          P<0.001 **                       | 
|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                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/15 (33%)       5/15 (33%)       2/15 (13%)       3/15 (20%)       7/15 (47%)                       | 
|POLY-3 RATE (b)    |        5/15.00          5/15.00          2/15.00          3/15.00          7/15.00                          | 
|POLY-3 PERCENT (g) |        33.3%            33.3%            13.3%            20.0%            46.7%                            | 
|TERMINAL (d)       |        5/15 (33%)       5/15 (33%)       2/15 (13%)       3/15 (20%)       7/15 (47%)                       | 
|FIRST INCIDENCE    |        189 (T)          189 (T)          189 (T)          189 (T)          189 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.211          P=0.648          P=0.198N         P=0.342N         P=0.357                          | 
|POLY 3             |        P=0.210          P=0.646          P=0.195N         P=0.343N         P=0.358                          | 
|POLY 1.5           |        P=0.210          P=0.646          P=0.195N         P=0.343N         P=0.358                          | 
|POLY 6             |        P=0.210          P=0.646          P=0.195N         P=0.343N         P=0.358                          | 
|LOGISTIC REGRESSION|        P=0.211          P=0.648          P=0.198N         P=0.342N         P=0.357                          | 
|COCH-ARM / FISHERS |        P=0.210          P=0.650N         P=0.195N         P=0.341N         P=0.355                          | 
|ORDER RESTRICTED   |        P=0.156          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 18      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen: Lymphoid Follicle                                                                                                        | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        15/15 (100%)     14/15 (93%)                      | 
|POLY-3 RATE (b)    |        0/15.00          0/15.00          0/15.00          15/15.00         14/14.00                         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             100.0%           100.0%                           | 
|TERMINAL (d)       |        0/15 (0%)        0/15 (0%)        0/15 (0%)        15/15 (100%)     14/14 (100%)                     | 
|FIRST INCIDENCE    |        ---              ---              ---              188 (T)          188 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 3             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 6             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P<0.001 **       P<0.001 **                       | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|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                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen: Lymphoid Follicle                                                                                                        | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        1/15 (7%)        1/15 (7%)        0/15 (0%)        1/15 (7%)                        | 
|POLY-3 RATE (b)    |        0/15.00          1/15.00          1/15.00          0/15.00          1/15.00                          | 
|POLY-3 PERCENT (g) |        0.0%             6.7%             6.7%             0.0%             6.7%                             | 
|TERMINAL (d)       |        0/15 (0%)        1/15 (7%)        1/15 (7%)        0/15 (0%)        1/15 (7%)                        | 
|FIRST INCIDENCE    |        ---              189 (T)          189 (T)          ---              189 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.500          P=0.500          P=0.500          (e)              P=0.500                          | 
|POLY 3             |        P=0.500          P=0.500          P=0.500          (e)              P=0.500                          | 
|POLY 1.5           |        P=0.500          P=0.500          P=0.500          (e)              P=0.500                          | 
|POLY 6             |        P=0.500          P=0.500          P=0.500          (e)              P=0.500                          | 
|LOGISTIC REGRESSION|        (e)              P=0.500          P=0.500          (e)              P=0.500                          | 
|COCH-ARM / FISHERS |        P=0.500          P=0.500          P=0.500          (e)              P=0.500                          | 
|ORDER RESTRICTED   |        P=0.312          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 19      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        3/15 (20%)                       | 
|POLY-3 RATE (b)    |        1/15.00          0/15.00          0/15.00          0/15.00          3/15.00                          | 
|POLY-3 PERCENT (g) |        6.7%             0.0%             0.0%             0.0%             20.0%                            | 
|TERMINAL (d)       |        1/15 (7%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        2/14 (14%)                       | 
|FIRST INCIDENCE    |        188 (T)          ---              ---              ---              11                               | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.033 *        P=0.500N         P=0.500N         P=0.500N         P=0.285                          | 
|POLY 3             |        P=0.031 *        P=0.500N         P=0.500N         P=0.500N         P=0.298                          | 
|POLY 1.5           |        P=0.031 *        P=0.500N         P=0.500N         P=0.500N         P=0.298                          | 
|POLY 6             |        P=0.031 *        P=0.500N         P=0.500N         P=0.500N         P=0.298                          | 
|LOGISTIC REGRESSION|        P=0.033 *        (e)              (e)              (e)              (e)                              | 
|COCH-ARM / FISHERS |        P=0.035 *        P=0.500N         P=0.500N         P=0.500N         P=0.299                          | 
|ORDER RESTRICTED   |        P=0.014 *        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        1/15.00          0/15.00          0/15.00          0/15.00          0/15.00                          | 
|POLY-3 PERCENT (g) |        6.7%             0.0%             0.0%             0.0%             0.0%                             | 
|TERMINAL (d)       |        1/15 (7%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)                        | 
|FIRST INCIDENCE    |        189 (T)          ---              ---              ---              ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.362N         P=0.500N         P=0.500N         P=0.500N         P=0.500N                         | 
|POLY 3             |        P=0.362N         P=0.500N         P=0.500N         P=0.500N         P=0.500N                         | 
|POLY 1.5           |        P=0.362N         P=0.500N         P=0.500N         P=0.500N         P=0.500N                         | 
|POLY 6             |        P=0.362N         P=0.500N         P=0.500N         P=0.500N         P=0.500N                         | 
|LOGISTIC REGRESSION|        P=0.362N         (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=0.087N         (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 20      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          25 MG/KG         50 MG/KG         100              200                              | 
|                   |                                                           MG/KG            MG/KG                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        0/15.00          0/15.00          0/15.00          0/15.00          0/14.00                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%                             | 
|TERMINAL (d)       |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/14 (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                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Stomach, Forestomach                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        3/15 (20%)       0/15 (0%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        0/15.00          0/15.00          3/15.00          0/15.00          0/15.00                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             20.0%            0.0%             0.0%                             | 
|TERMINAL (d)       |        0/15 (0%)        0/15 (0%)        3/15 (20%)       0/15 (0%)        0/15 (0%)                        | 
|FIRST INCIDENCE    |        ---              ---              189 (T)          ---              ---                              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.418N         (e)              P=0.116          (e)              (e)                              | 
|POLY 3             |        P=0.413N         (e)              P=0.106          (e)              (e)                              | 
|POLY 1.5           |        P=0.413N         (e)              P=0.106          (e)              (e)                              | 
|POLY 6             |        P=0.413N         (e)              P=0.106          (e)              (e)                              | 
|LOGISTIC REGRESSION|        (e)              (e)              P=0.116          (e)              (e)                              | 
|COCH-ARM / FISHERS |        P=0.417N         (e)              P=0.112          (e)              (e)                              | 
|ORDER RESTRICTED   |        P=0.278          (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 21      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|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%)        0/15 (0%)        0/15 (0%)        7/15 (47%)       13/15 (87%)                      | 
|POLY-3 RATE (b)    |        0/15.00          0/15.00          0/15.00          7/15.00          13/14.00                         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             46.7%            92.9%                            | 
|TERMINAL (d)       |        0/15 (0%)        0/15 (0%)        0/15 (0%)        7/15 (47%)       13/14 (93%)                      | 
|FIRST INCIDENCE    |        ---              ---              ---              188 (T)          188 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.005 **       P<0.001 **                       | 
|POLY 3             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 6             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.005 **       P<0.001 **                       | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P=0.003 **       P<0.001 **                       | 
|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                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)                        | 
|POLY-3 RATE (b)    |        0/15.00          0/15.00          0/15.00          0/15.00          0/15.00                          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%                             | 
|TERMINAL (d)       |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (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:  11/05/03                           EXPERIMENT: 99034 TEST: 01                                            Page 22      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -         TRANSGENIC MODEL EVALUATION II (
BEN                                                                                                                                 
                                         Terminal Sacrifice at 27 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)        |        12/15 (80%)      15/15 (100%)     15/15 (100%)     15/15 (100%)     14/15 (93%)                      | 
|POLY-3 RATE (b)    |        12/15.00         15/15.00         15/15.00         15/15.00         14/15.00                         | 
|POLY-3 PERCENT (g) |        80.0%            100.0%           100.0%           100.0%           93.3%                            | 
|TERMINAL (d)       |        12/15 (80%)      15/15 (100%)     15/15 (100%)     15/15 (100%)     14/15 (93%)                      | 
|FIRST INCIDENCE    |        189 (T)          189 (T)          189 (T)          189 (T)          189 (T)                          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.359          P=0.116          P=0.116          P=0.116          P=0.299                          | 
|POLY 3             |        P=0.354          P=0.106          P=0.106          P=0.106          P=0.298                          | 
|POLY 1.5           |        P=0.354          P=0.106          P=0.106          P=0.106          P=0.298                          | 
|POLY 6             |        P=0.354          P=0.106          P=0.106          P=0.106          P=0.298                          | 
|LOGISTIC REGRESSION|        P=0.359          P=0.116          P=0.116          P=0.116          P=0.299                          | 
|COCH-ARM / FISHERS |        P=0.358          P=0.112          P=0.112          P=0.112          P=0.299                          | 
|ORDER RESTRICTED   |        P=0.014 *        (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
(a)  Number of tumor-bearing animals /  number of animals examined at site.                                                         
                                                                                                                                   
(b)  Number of tumor-bearing animals / Poly-3 number                                                                                
(d)  Observed incidence at terminal kill.                                                                                           
(f)  Beneath the control incidence are the P-values associated with the trend                                                       
test.  Beneath the dosed group incidence are the P-values corresponding to                                                          
pairwise comparisons between the controls and that dosed group.  The life                                                           
table analysis regards tumors in animals dying prior to  terminal kill as                                                           
 being (directly or indirectly) the cause of death.                                                                                 
Logistic regression is an alternative                                                                                               
 method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage                                                       
and Fishers exact tests compare directly the overall incidence rates                                                                
For all tests a negative trend is indicated by N                                                                                    
(e)  Value of Statistic cannot be computed.                                                                                         
(g)  Poly-3 adjusted lifetime tumor incidence.                                                                                      
(I)  Interim sacrifice                                                                                                              
(T)  Terminal sacrifice                                                                                                             
#   Tumor rates based on number of animals necropsied.                                                                              
*   To the right of any statistical result, indicates significance at (P<=0.05).                                                    
**  To the right of any statistical result, indicates significance at (P<=0.01).                                                    
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.