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).