National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/17451

TDMS Study 99036-01 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                      TRANSGENIC MODEL EVALUATION II (PHENOLPHTHALEIN)                   DATE: 04/21/04       
EXPERIMENT: 99036 TEST: 01                                                                                     TIME: 08:36:55       
TEST TYPE:  SUBCHRON 26-WEEK                    CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-65406                              ROUTE: DOSED FEED                                              NTP C#: C99036       
PATHOLOGIST: MISSING                                                                                           CAS: 77-09-08        
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                           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 (PHENOLPHTHALEIN)                   DATE: 04/21/04       
EXPERIMENT: 99036 TEST: 01                                                                                     TIME: 08:36:55       
TEST TYPE:  SUBCHRON 26-WEEK                    CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-65406                              ROUTE: DOSED FEED                                              NTP C#: C99036       
PATHOLOGIST: MISSING                                                                                           CAS: 77-09-08        
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF    TRANSGENIC MODEL EVALUATION II (PHENOLP                                                                       
===============================================================                                                                     
Male Mice                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Adrenal Cortex                         Hyperplasia Focal                                                                            
                                       Hypertrophy Focal                                                                            
Epididymis                             Hypospermia                                                                                  
Kidney                                 Nephropathy                                                                                  
Kidney: Renal Tubule                   Hypertrophy                                                                                  
Liver                                  Inflammation Chronic                                                                         
Spleen                                 Hematopoietic Cell Proliferation                                                             
Testes: Germinal Epithelium            Atrophy                                                                                      
Testes: Interstitial Cell              Hyperplasia                                                                                  
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Lymph Node, Mandibular                 Hyperplasia Lymphoid                                                                         
Spleen                                 Hematopoietic Cell Proliferation                                                             
Thymus                                 Hyperplasia Atypical                                                                         
===============================================================                                                                     
                                                                                                                                   
       Date:  04/21/04                           EXPERIMENT: 99036 TEST: 01                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions in        Mice(P16(INK4A)/(+/-) (C57BL/6))  -     TRANSGENIC MODEL EVALUATION II (PHE
NOLP                                                                                                                                
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/14 (0%)        0/15 (0%)        0/15 (0%)        4/14 (29%)       1/15 (7%)        0/14 (0%)       | 
|POLY-3 RATE (b)    |        0/13.07          0/15.00          0/15.00          4/13.01          1/15.00          0/14.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             30.7%            6.7%             0.0%            | 
|TERMINAL (d)       |        0/13 (0%)        0/15 (0%)        0/15 (0%)        4/13 (31%)       1/15 (7%)        0/14 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              183 (T)          183 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.369N         (e)              (e)              P=0.055          P=0.529          (e)             | 
|POLY 3             |        P=0.371N         (e)              (e)              P=0.042 *        P=0.527          (e)             | 
|POLY 1.5           |        P=0.372N         (e)              (e)              P=0.041 *        P=0.524          (e)             | 
|POLY 6             |        P=0.370N         (e)              (e)              P=0.042 *        P=0.528          (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.055          P=0.529          (e)             | 
|COCH-ARM / FISHERS |        P=0.378N         (e)              (e)              P=0.049 *        P=0.517          (e)             | 
|ORDER RESTRICTED   |        P=0.141          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/14 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/15.00          0/13.00          0/14.00          0/15.00          0/14.00          0/15.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/15 (0%)        0/13 (0%)        0/14 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/21/04                           EXPERIMENT: 99036 TEST: 01                                            Page 2       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -     TRANSGENIC MODEL EVALUATION II (PHEN
OLP                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/14 (29%)       3/15 (20%)       1/15 (7%)        1/14 (7%)        2/15 (13%)       0/14 (0%)       | 
|POLY-3 RATE (b)    |        4/13.07          3/15.00          1/15.00          1/13.01          2/15.00          0/14.00         | 
|POLY-3 PERCENT (g) |        30.6%            20.0%            6.7%             7.7%             13.3%            0.0%            | 
|TERMINAL (d)       |        4/13 (31%)       3/15 (20%)       1/15 (7%)        1/13 (8%)        2/15 (13%)       0/14 (0%)       | 
|FIRST INCIDENCE    |        183 (T)          183 (T)          183 (T)          183 (T)          183 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.090N         P=0.415N         P=0.126N         P=0.165N         P=0.259N         P=0.047N*       | 
|POLY 3             |        P=0.088N         P=0.419N         P=0.121N         P=0.160N         P=0.261N         P=0.035N*       | 
|POLY 1.5           |        P=0.089N         P=0.428N         P=0.125N         P=0.163N         P=0.267N         P=0.037N*       | 
|POLY 6             |        P=0.088N         P=0.416N         P=0.119N         P=0.159N         P=0.258N         P=0.035N*       | 
|LOGISTIC REGRESSION|        P=0.090N         P=0.415N         P=0.126N         P=0.160N         P=0.259N         (e)             | 
|COCH-ARM / FISHERS |        P=0.095N         P=0.458N         P=0.143N         P=0.163N         P=0.291N         P=0.049N*       | 
|ORDER RESTRICTED   |        P=0.013N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/14 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/15.00          0/13.00          0/14.00          0/15.00          0/14.00          0/15.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/15 (0%)        0/13 (0%)        0/14 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/21/04                           EXPERIMENT: 99036 TEST: 01                                            Page 3       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -     TRANSGENIC MODEL EVALUATION II (PHEN
OLP                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Epididymis                                                                                                                       | 
|     Hypospermia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        1/15 (7%)        0/15 (0%)        15/15 (100%)     14/15 (93%)     | 
|POLY-3 RATE (b)    |        0/13.07          0/15.00          1/15.00          0/13.01          15/15.00         14/14.00        | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             6.7%             0.0%             100.0%           100.0%          | 
|TERMINAL (d)       |        0/13 (0%)        0/15 (0%)        1/15 (7%)        0/13 (0%)        15/15 (100%)     14/14 (100%)    | 
|FIRST INCIDENCE    |        ---              ---              183 (T)          ---              183 (T)          183 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              P=0.529          (e)              P<0.001 **       P<0.001 **      | 
|POLY 3             |        P<0.001 **       (e)              P=0.527          (e)              P<0.001 **       P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       (e)              P=0.524          (e)              P<0.001 **       P<0.001 **      | 
|POLY 6             |        P<0.001 **       (e)              P=0.528          (e)              P<0.001 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        (e)              (e)              P=0.529          (e)              P<0.001 **       P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              P=0.500          (e)              P<0.001 **       P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Epididymis                                                                                                                       | 
|     Hypospermia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|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   |                                                                                                             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/21/04                           EXPERIMENT: 99036 TEST: 01                                            Page 4       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -     TRANSGENIC MODEL EVALUATION II (PHEN
OLP                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        6/14 (43%)       7/15 (47%)       8/15 (53%)       6/14 (43%)       15/15 (100%)     14/15 (93%)     | 
|POLY-3 RATE (b)    |        6/13.07          7/15.00          8/15.00          6/13.01          15/15.00         14/14.00        | 
|POLY-3 PERCENT (g) |        45.9%            46.7%            53.3%            46.1%            100.0%           100.0%          | 
|TERMINAL (d)       |        6/13 (46%)       7/15 (47%)       8/15 (53%)       6/13 (46%)       15/15 (100%)     14/14 (100%)    | 
|FIRST INCIDENCE    |        183 (T)          183 (T)          183 (T)          183 (T)          183 (T)          183 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.635          P=0.500          P=0.650          P=0.003 **       P=0.003 **      | 
|POLY 3             |        P<0.001 **       P=0.628          P=0.494          P=0.644          P<0.001 **       P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       P=0.615          P=0.479          P=0.638          P<0.001 **       P<0.001 **      | 
|POLY 6             |        P<0.001 **       P=0.633          P=0.500          P=0.647          P<0.001 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        P<0.001 **       P=0.635          P=0.500          P=0.650          P=0.003 **       P=0.003 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.566          P=0.424          P=0.648N         P<0.001 **       P=0.005 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        10/15 (67%)      6/15 (40%)       8/15 (53%)       8/15 (53%)       7/15 (47%)       11/15 (73%)     | 
|POLY-3 RATE (b)    |        10/15.00         6/13.00          8/14.00          8/15.00          7/14.00          11/15.00        | 
|POLY-3 PERCENT (g) |        66.7%            46.2%            57.1%            53.3%            50.0%            73.3%           | 
|TERMINAL (d)       |        10/15 (67%)      6/13 (46%)       8/14 (57%)       8/15 (53%)       7/14 (50%)       11/15 (73%)     | 
|FIRST INCIDENCE    |        184 (T)          184 (T)          184 (T)          184 (T)          184 (T)          184 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.177          P=0.243N         P=0.443N         P=0.357N         P=0.300N         P=0.500         | 
|POLY 3             |        P=0.180          P=0.243N         P=0.444N         P=0.358N         P=0.301N         P=0.500         | 
|POLY 1.5           |        P=0.179          P=0.239N         P=0.442N         P=0.358N         P=0.297N         P=0.500         | 
|POLY 6             |        P=0.180          P=0.243N         P=0.444N         P=0.358N         P=0.301N         P=0.500         | 
|LOGISTIC REGRESSION|        P=0.177          P=0.243N         P=0.443N         P=0.357N         P=0.300N         P=0.500         | 
|COCH-ARM / FISHERS |        P=0.130          P=0.136N         P=0.355N         P=0.355N         P=0.231N         P=0.500         | 
|ORDER RESTRICTED   |        P=0.270          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/21/04                           EXPERIMENT: 99036 TEST: 01                                            Page 5       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -     TRANSGENIC MODEL EVALUATION II (PHEN
OLP                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/14 (0%)        0/15 (0%)        0/15 (0%)        10/14 (71%)      15/15 (100%)     14/15 (93%)     | 
|POLY-3 RATE (b)    |        0/13.07          0/15.00          0/15.00          10/13.01         15/15.00         14/14.00        | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             76.9%            100.0%           100.0%          | 
|TERMINAL (d)       |        0/13 (0%)        0/15 (0%)        0/15 (0%)        10/13 (77%)      15/15 (100%)     14/14 (100%)    | 
|FIRST INCIDENCE    |        ---              ---              ---              183 (T)          183 (T)          183 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 3             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 6             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P<0.001 **       P<0.001 **       P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **       P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/15.00          0/13.00          0/14.00          0/15.00          0/14.00          0/15.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/15 (0%)        0/13 (0%)        0/14 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/21/04                           EXPERIMENT: 99036 TEST: 01                                            Page 6       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -     TRANSGENIC MODEL EVALUATION II (PHEN
OLP                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        11/15 (73%)      8/15 (53%)       7/15 (47%)       9/14 (64%)       10/15 (67%)      5/14 (36%)      | 
|POLY-3 RATE (b)    |        11/13.07         8/15.00          7/15.00          9/13.01          10/15.00         5/14.00         | 
|POLY-3 PERCENT (g) |        84.2%            53.3%            46.7%            69.2%            66.7%            35.7%           | 
|TERMINAL (d)       |        11/13 (85%)      8/15 (53%)       7/15 (47%)       9/13 (69%)       10/15 (67%)      5/14 (36%)      | 
|FIRST INCIDENCE    |        183 (T)          183 (T)          183 (T)          183 (T)          183 (T)          183 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.057N         P=0.091N         P=0.048N*        P=0.324N         P=0.260N         P=0.016N*       | 
|POLY 3             |        P=0.058N         P=0.087N         P=0.041N*        P=0.332N         P=0.268N         P=0.009N**      | 
|POLY 1.5           |        P=0.061N         P=0.100N         P=0.048N*        P=0.349N         P=0.295N         P=0.011N*       | 
|POLY 6             |        P=0.058N         P=0.084N         P=0.039N*        P=0.325N         P=0.260N         P=0.008N**      | 
|LOGISTIC REGRESSION|        P=0.057N         P=0.091N         P=0.048N*        P=0.324N         P=0.260N         P=0.016N*       | 
|COCH-ARM / FISHERS |        P=0.088N         P=0.225N         P=0.132N         P=0.450N         P=0.500N         P=0.048N*       | 
|ORDER RESTRICTED   |        P=0.008N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        10/15 (67%)      8/15 (53%)       12/15 (80%)      10/15 (67%)      7/15 (47%)       8/15 (53%)      | 
|POLY-3 RATE (b)    |        10/15.00         8/13.00          12/14.00         10/15.00         7/14.00          8/15.00         | 
|POLY-3 PERCENT (g) |        66.7%            61.5%            85.7%            66.7%            50.0%            53.3%           | 
|TERMINAL (d)       |        10/15 (67%)      8/13 (62%)       12/14 (86%)      10/15 (67%)      7/14 (50%)       8/15 (53%)      | 
|FIRST INCIDENCE    |        184 (T)          184 (T)          184 (T)          184 (T)          184 (T)          184 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.163N         P=0.544N         P=0.227          P=0.648          P=0.300N         P=0.357N        | 
|POLY 3             |        P=0.162N         P=0.543N         P=0.225          P=0.646          P=0.301N         P=0.358N        | 
|POLY 1.5           |        P=0.163N         P=0.537N         P=0.228          P=0.646          P=0.297N         P=0.358N        | 
|POLY 6             |        P=0.162N         P=0.543N         P=0.225          P=0.646          P=0.301N         P=0.358N        | 
|LOGISTIC REGRESSION|        P=0.163N         P=0.544N         P=0.223          P=0.648          P=0.300N         P=0.357N        | 
|COCH-ARM / FISHERS |        P=0.231N         P=0.355N         P=0.341          P=0.650N         P=0.231N         P=0.355N        | 
|ORDER RESTRICTED   |        P=0.220N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/21/04                           EXPERIMENT: 99036 TEST: 01                                            Page 7       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -     TRANSGENIC MODEL EVALUATION II (PHEN
OLP                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        2/15 (13%)       0/15 (0%)        2/14 (14%)       1/15 (7%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/13.07          2/15.00          0/15.00          2/12.01          1/15.00          0/14.00         | 
|POLY-3 PERCENT (g) |        0.0%             13.3%            0.0%             16.7%            6.7%             0.0%            | 
|TERMINAL (d)       |        0/13 (0%)        2/15 (13%)       0/15 (0%)        2/12 (17%)       1/15 (7%)        0/14 (0%)       | 
|FIRST INCIDENCE    |        ---              183 (T)          ---              183 (T)          183 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.321N         P=0.268          (e)              P=0.217          P=0.529          (e)             | 
|POLY 3             |        P=0.321N         P=0.264          (e)              P=0.210          P=0.527          (e)             | 
|POLY 1.5           |        P=0.322N         P=0.260          (e)              P=0.209          P=0.524          (e)             | 
|POLY 6             |        P=0.321N         P=0.266          (e)              P=0.211          P=0.528          (e)             | 
|LOGISTIC REGRESSION|        (e)              P=0.268          (e)              P=0.217          P=0.529          (e)             | 
|COCH-ARM / FISHERS |        P=0.322N         P=0.241          (e)              P=0.224          P=0.500          (e)             | 
|ORDER RESTRICTED   |        P=0.391          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/15 (13%)       1/15 (7%)        1/15 (7%)        3/15 (20%)       1/15 (7%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        2/15.00          1/13.00          1/14.00          3/15.00          1/14.00          0/15.00         | 
|POLY-3 PERCENT (g) |        13.3%            7.7%             7.1%             20.0%            7.1%             0.0%            | 
|TERMINAL (d)       |        2/15 (13%)       1/13 (8%)        1/14 (7%)        3/15 (20%)       1/14 (7%)        0/15 (0%)       | 
|FIRST INCIDENCE    |        184 (T)          184 (T)          184 (T)          184 (T)          184 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.152N         P=0.551N         P=0.525N         P=0.500          P=0.525N         P=0.236N        | 
|POLY 3             |        P=0.144N         P=0.550N         P=0.524N         P=0.500          P=0.524N         P=0.232N        | 
|POLY 1.5           |        P=0.144N         P=0.549N         P=0.524N         P=0.500          P=0.523N         P=0.232N        | 
|POLY 6             |        P=0.144N         P=0.550N         P=0.524N         P=0.500          P=0.524N         P=0.232N        | 
|LOGISTIC REGRESSION|        P=0.152N         P=0.551N         P=0.525N         P=0.500          P=0.525N         (e)             | 
|COCH-ARM / FISHERS |        P=0.160N         P=0.500N         P=0.500N         P=0.500          P=0.500N         P=0.241N        | 
|ORDER RESTRICTED   |        P=0.174N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/21/04                           EXPERIMENT: 99036 TEST: 01                                            Page 8       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -     TRANSGENIC MODEL EVALUATION II (PHEN
OLP                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/14 (0%)        0/15 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)        0/13 (0%)       | 
|POLY-3 RATE (b)    |        0/13.07          0/15.00          0/15.00          0/13.01          0/15.00          0/13.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/13 (0%)        0/15 (0%)        0/15 (0%)        0/13 (0%)        0/15 (0%)        0/13 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        2/15 (13%)       0/15 (0%)        0/15 (0%)        2/15 (13%)       0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/15.00          2/15.00          0/14.00          0/15.00          2/15.00          0/15.00         | 
|POLY-3 PERCENT (g) |        0.0%             13.3%            0.0%             0.0%             13.3%            0.0%            | 
|TERMINAL (d)       |        0/15 (0%)        0/13 (0%)        0/14 (0%)        0/15 (0%)        1/14 (7%)        0/15 (0%)       | 
|FIRST INCIDENCE    |        ---              13               ---              ---              26               ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.490N         P=0.232          (e)              (e)              P=0.232          (e)             | 
|POLY 3             |        P=0.491N         P=0.232          (e)              (e)              P=0.232          (e)             | 
|POLY 1.5           |        P=0.491N         P=0.232          (e)              (e)              P=0.232          (e)             | 
|POLY 6             |        P=0.491N         P=0.232          (e)              (e)              P=0.232          (e)             | 
|LOGISTIC REGRESSION|        P=0.792          (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.501N         P=0.241          (e)              (e)              P=0.241          (e)             | 
|ORDER RESTRICTED   |        P=0.332          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/21/04                           EXPERIMENT: 99036 TEST: 01                                            Page 9       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -     TRANSGENIC MODEL EVALUATION II (PHEN
OLP                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/14 (14%)       1/15 (7%)        2/15 (13%)       0/14 (0%)        3/15 (20%)       1/13 (8%)       | 
|POLY-3 RATE (b)    |        2/13.07          1/15.00          2/15.00          0/13.01          3/15.00          1/13.00         | 
|POLY-3 PERCENT (g) |        15.3%            6.7%             13.3%            0.0%             20.0%            7.7%            | 
|TERMINAL (d)       |        2/13 (15%)       1/15 (7%)        2/15 (13%)       0/13 (0%)        3/15 (20%)       1/13 (8%)       | 
|FIRST INCIDENCE    |        183 (T)          183 (T)          183 (T)          ---              183 (T)          183 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.598N         P=0.449N         P=0.648N         P=0.235N         P=0.569          P=0.500N        | 
|POLY 3             |        P=0.597N         P=0.451N         P=0.647N         P=0.231N         P=0.565          P=0.502N        | 
|POLY 1.5           |        P=0.599N         P=0.456N         P=0.653N         P=0.233N         P=0.558          P=0.507N        | 
|POLY 6             |        P=0.597N         P=0.449N         P=0.645N         P=0.230N         P=0.567          P=0.500N        | 
|LOGISTIC REGRESSION|        P=0.598N         P=0.449N         P=0.648N         (e)              P=0.569          P=0.500N        | 
|COCH-ARM / FISHERS |        P=0.615N         P=0.473N         P=0.674N         P=0.241N         P=0.535          P=0.529N        | 
|ORDER RESTRICTED   |        P=0.501N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/15 (27%)       2/15 (13%)       2/15 (13%)       0/15 (0%)        1/15 (7%)        6/15 (40%)      | 
|POLY-3 RATE (b)    |        4/15.00          2/13.00          2/14.00          0/15.00          1/14.00          6/15.00         | 
|POLY-3 PERCENT (g) |        26.7%            15.4%            14.3%            0.0%             7.1%             40.0%           | 
|TERMINAL (d)       |        4/15 (27%)       2/13 (15%)       2/14 (14%)       0/15 (0%)        1/14 (7%)        6/15 (40%)      | 
|FIRST INCIDENCE    |        184 (T)          184 (T)          184 (T)          ---              184 (T)          184 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.027 *        P=0.398N         P=0.360N         P=0.057N         P=0.189N         P=0.352         | 
|POLY 3             |        P=0.021 *        P=0.399N         P=0.361N         P=0.045N*        P=0.185N         P=0.353         | 
|POLY 1.5           |        P=0.020 *        P=0.397N         P=0.360N         P=0.045N*        P=0.184N         P=0.353         | 
|POLY 6             |        P=0.021 *        P=0.399N         P=0.361N         P=0.045N*        P=0.185N         P=0.353         | 
|LOGISTIC REGRESSION|        P=0.027 *        P=0.398N         P=0.360N         (e)              P=0.184N         P=0.352         | 
|COCH-ARM / FISHERS |        P=0.021 *        P=0.326N         P=0.326N         P=0.050N         P=0.165N         P=0.350         | 
|ORDER RESTRICTED   |        P=0.026 *        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/21/04                           EXPERIMENT: 99036 TEST: 01                                            Page 10      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -     TRANSGENIC MODEL EVALUATION II (PHEN
OLP                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/14 (0%)        1/15 (7%)        1/15 (7%)        1/14 (7%)        0/15 (0%)        0/14 (0%)       | 
|POLY-3 RATE (b)    |        0/13.07          1/15.00          1/15.00          1/14.00          0/15.00          0/14.00         | 
|POLY-3 PERCENT (g) |        0.0%             6.7%             6.7%             7.1%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/13 (0%)        1/15 (7%)        1/15 (7%)        0/13 (0%)        0/15 (0%)        0/14 (0%)       | 
|FIRST INCIDENCE    |        ---              183 (T)          183 (T)          43               ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.377N         P=0.529          P=0.529          P=0.500          (e)              (e)             | 
|POLY 3             |        P=0.373N         P=0.527          P=0.527          P=0.514          (e)              (e)             | 
|POLY 1.5           |        P=0.375N         P=0.524          P=0.524          P=0.511          (e)              (e)             | 
|POLY 6             |        P=0.373N         P=0.528          P=0.528          P=0.515          (e)              (e)             | 
|LOGISTIC REGRESSION|        P=0.510N         P=0.529          P=0.529          (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.381N         P=0.517          P=0.517          P=0.500          (e)              (e)             | 
|ORDER RESTRICTED   |        P=0.436N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        1/14 (7%)        1/15 (7%)        0/15 (0%)        2/15 (13%)       2/15 (13%)      | 
|POLY-3 RATE (b)    |        1/15.00          1/14.00          1/15.00          0/15.00          2/15.00          2/15.00         | 
|POLY-3 PERCENT (g) |        6.7%             7.1%             6.7%             0.0%             13.3%            13.3%           | 
|TERMINAL (d)       |        1/15 (7%)        0/13 (0%)        0/14 (0%)        0/15 (0%)        1/14 (7%)        2/15 (13%)      | 
|FIRST INCIDENCE    |        184 (T)          21               15               ---              26               184 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.282          P=0.737          P=0.753          P=0.500N         P=0.484          P=0.500         | 
|POLY 3             |        P=0.269          P=0.745          P=0.760          P=0.500N         P=0.500          P=0.500         | 
|POLY 1.5           |        P=0.269          P=0.745          P=0.760          P=0.500N         P=0.500          P=0.500         | 
|POLY 6             |        P=0.269          P=0.745          P=0.760          P=0.500N         P=0.500          P=0.500         | 
|LOGISTIC REGRESSION|        P=0.282          (e)              (e)              (e)              (e)              P=0.500         | 
|COCH-ARM / FISHERS |        P=0.265          P=0.741          P=0.759N         P=0.500N         P=0.500          P=0.500         | 
|ORDER RESTRICTED   |        P=0.370          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/21/04                           EXPERIMENT: 99036 TEST: 01                                            Page 11      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -     TRANSGENIC MODEL EVALUATION II (PHEN
OLP                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/14 (0%)        0/15 (0%)        1/15 (7%)        0/14 (0%)        2/15 (13%)       1/14 (7%)       | 
|POLY-3 RATE (b)    |        0/13.07          0/15.00          1/15.00          0/13.01          2/15.00          1/14.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             6.7%             0.0%             13.3%            7.1%            | 
|TERMINAL (d)       |        0/13 (0%)        0/15 (0%)        1/15 (7%)        0/13 (0%)        2/15 (13%)       1/14 (7%)       | 
|FIRST INCIDENCE    |        ---              ---              183 (T)          ---              183 (T)          183 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.360          (e)              P=0.529          (e)              P=0.268          P=0.515         | 
|POLY 3             |        P=0.367          (e)              P=0.527          (e)              P=0.264          P=0.514         | 
|POLY 1.5           |        P=0.364          (e)              P=0.524          (e)              P=0.260          P=0.511         | 
|POLY 6             |        P=0.368          (e)              P=0.528          (e)              P=0.265          P=0.515         | 
|LOGISTIC REGRESSION|        (e)              (e)              P=0.529          (e)              P=0.268          P=0.515         | 
|COCH-ARM / FISHERS |        P=0.348          (e)              P=0.517          (e)              P=0.259          P=0.500         | 
|ORDER RESTRICTED   |        P=0.188          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mesenteric                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/14 (0%)        1/15 (7%)        0/15 (0%)        0/15 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/15.00          0/13.00          1/14.00          0/15.00          0/14.00          0/15.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             7.1%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/15 (0%)        0/13 (0%)        1/14 (7%)        0/15 (0%)        0/14 (0%)        0/15 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              184 (T)          ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.683N         (e)              P=0.486          (e)              (e)              (e)             | 
|POLY 3             |        P=0.697N         (e)              P=0.486          (e)              (e)              (e)             | 
|POLY 1.5           |        P=0.696N         (e)              P=0.487          (e)              (e)              (e)             | 
|POLY 6             |        P=0.697N         (e)              P=0.486          (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              P=0.486          (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.691N         (e)              P=0.500          (e)              (e)              (e)             | 
|ORDER RESTRICTED   |        P=0.490N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/21/04                           EXPERIMENT: 99036 TEST: 01                                            Page 12      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -     TRANSGENIC MODEL EVALUATION II (PHEN
OLP                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/14 (14%)       5/15 (33%)       3/15 (20%)       1/14 (7%)        2/15 (13%)       14/14 (100%)    | 
|POLY-3 RATE (b)    |        2/13.07          5/15.00          3/15.00          1/13.01          2/15.00          14/14.00        | 
|POLY-3 PERCENT (g) |        15.3%            33.3%            20.0%            7.7%             13.3%            100.0%          | 
|TERMINAL (d)       |        2/13 (15%)       5/15 (33%)       3/15 (20%)       1/13 (8%)        2/15 (13%)       14/14 (100%)    | 
|FIRST INCIDENCE    |        183 (T)          183 (T)          183 (T)          183 (T)          183 (T)          183 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.260          P=0.569          P=0.500N         P=0.648N         P<0.001 **      | 
|POLY 3             |        P<0.001 **       P=0.257          P=0.565          P=0.502N         P=0.647N         P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       P=0.249          P=0.558          P=0.504N         P=0.653N         P<0.001 **      | 
|POLY 6             |        P<0.001 **       P=0.259          P=0.567          P=0.500N         P=0.645N         P<0.001 **      | 
|LOGISTIC REGRESSION|        P<0.001 **       P=0.260          P=0.569          P=0.500N         P=0.648N         P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.224          P=0.535          P=0.500N         P=0.674N         P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/15 (13%)       5/14 (36%)       9/14 (64%)       8/15 (53%)       7/15 (47%)       13/15 (87%)     | 
|POLY-3 RATE (b)    |        2/15.00          5/13.00          9/14.00          8/15.00          7/14.00          13/15.00        | 
|POLY-3 PERCENT (g) |        13.3%            38.5%            64.3%            53.3%            50.0%            86.7%           | 
|TERMINAL (d)       |        2/15 (13%)       5/13 (39%)       9/14 (64%)       8/15 (53%)       7/14 (50%)       13/15 (87%)     | 
|FIRST INCIDENCE    |        184 (T)          184 (T)          184 (T)          184 (T)          184 (T)          184 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.002 **       P=0.141          P=0.008 **       P=0.028 *        P=0.044 *        P<0.001 **      | 
|POLY 3             |        P<0.001 **       P=0.136          P=0.003 **       P=0.019 *        P=0.035 *        P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       P=0.137          P=0.003 **       P=0.019 *        P=0.036 *        P<0.001 **      | 
|POLY 6             |        P<0.001 **       P=0.136          P=0.003 **       P=0.019 *        P=0.035 *        P<0.001 **      | 
|LOGISTIC REGRESSION|        P=0.002 **       P=0.141          P=0.008 **       P=0.028 *        P=0.044 *        P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.166          P=0.007 **       P=0.025 *        P=0.054          P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/21/04                           EXPERIMENT: 99036 TEST: 01                                            Page 13      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -     TRANSGENIC MODEL EVALUATION II (PHEN
OLP                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen: Lymphoid Follicle                                                                                                        | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/14 (0%)        0/15 (0%)        0/15 (0%)        1/14 (7%)        0/15 (0%)        0/14 (0%)       | 
|POLY-3 RATE (b)    |        0/13.07          0/15.00          0/15.00          1/14.00          0/15.00          0/14.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             7.1%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/13 (0%)        0/15 (0%)        0/15 (0%)        0/13 (0%)        0/15 (0%)        0/14 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              43               ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.730N         (e)              (e)              P=0.500          (e)              (e)             | 
|POLY 3             |        P=0.727N         (e)              (e)              P=0.514          (e)              (e)             | 
|POLY 1.5           |        P=0.728N         (e)              (e)              P=0.511          (e)              (e)             | 
|POLY 6             |        P=0.727N         (e)              (e)              P=0.515          (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.731N         (e)              (e)              P=0.500          (e)              (e)             | 
|ORDER RESTRICTED   |        P=0.533          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen: Lymphoid Follicle                                                                                                        | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        1/14 (7%)        0/14 (0%)        0/15 (0%)        2/15 (13%)       0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/15.00          1/14.00          0/14.00          0/15.00          2/15.00          0/15.00         | 
|POLY-3 PERCENT (g) |        0.0%             7.1%             0.0%             0.0%             13.3%            0.0%            | 
|TERMINAL (d)       |        0/15 (0%)        0/13 (0%)        0/14 (0%)        0/15 (0%)        1/14 (7%)        0/15 (0%)       | 
|FIRST INCIDENCE    |        ---              21               ---              ---              26               ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.621N         P=0.486          (e)              (e)              P=0.232          (e)             | 
|POLY 3             |        P=0.628N         P=0.486          (e)              (e)              P=0.232          (e)             | 
|POLY 1.5           |        P=0.628N         P=0.486          (e)              (e)              P=0.232          (e)             | 
|POLY 6             |        P=0.628N         P=0.486          (e)              (e)              P=0.232          (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.627N         P=0.483          (e)              (e)              P=0.241          (e)             | 
|ORDER RESTRICTED   |        P=0.271          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/21/04                           EXPERIMENT: 99036 TEST: 01                                            Page 14      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -     TRANSGENIC MODEL EVALUATION II (PHEN
OLP                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Germinal Epithelium                                                                                                      | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        1/15 (7%)        1/15 (7%)        0/15 (0%)        15/15 (100%)     14/15 (93%)     | 
|POLY-3 RATE (b)    |        0/13.07          1/15.00          1/15.00          0/13.01          15/15.00         14/14.00        | 
|POLY-3 PERCENT (g) |        0.0%             6.7%             6.7%             0.0%             100.0%           100.0%          | 
|TERMINAL (d)       |        0/13 (0%)        1/15 (7%)        1/15 (7%)        0/13 (0%)        15/15 (100%)     14/14 (100%)    | 
|FIRST INCIDENCE    |        ---              183 (T)          183 (T)          ---              183 (T)          183 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.529          P=0.529          (e)              P<0.001 **       P<0.001 **      | 
|POLY 3             |        P<0.001 **       P=0.527          P=0.527          (e)              P<0.001 **       P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       P=0.524          P=0.524          (e)              P<0.001 **       P<0.001 **      | 
|POLY 6             |        P<0.001 **       P=0.528          P=0.528          (e)              P<0.001 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        (e)              P=0.529          P=0.529          (e)              P<0.001 **       P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.500          P=0.500          (e)              P<0.001 **       P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Germinal Epithelium                                                                                                      | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|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   |                                                                                                             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/21/04                           EXPERIMENT: 99036 TEST: 01                                            Page 15      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -     TRANSGENIC MODEL EVALUATION II (PHEN
OLP                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Interstitial Cell                                                                                                        | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        1/15 (7%)        1/15 (7%)        0/15 (0%)        15/15 (100%)     14/15 (93%)     | 
|POLY-3 RATE (b)    |        0/13.07          1/15.00          1/15.00          0/13.01          15/15.00         14/14.00        | 
|POLY-3 PERCENT (g) |        0.0%             6.7%             6.7%             0.0%             100.0%           100.0%          | 
|TERMINAL (d)       |        0/13 (0%)        1/15 (7%)        1/15 (7%)        0/13 (0%)        15/15 (100%)     14/14 (100%)    | 
|FIRST INCIDENCE    |        ---              183 (T)          183 (T)          ---              183 (T)          183 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.529          P=0.529          (e)              P<0.001 **       P<0.001 **      | 
|POLY 3             |        P<0.001 **       P=0.527          P=0.527          (e)              P<0.001 **       P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       P=0.524          P=0.524          (e)              P<0.001 **       P<0.001 **      | 
|POLY 6             |        P<0.001 **       P=0.528          P=0.528          (e)              P<0.001 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        (e)              P=0.529          P=0.529          (e)              P<0.001 **       P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.500          P=0.500          (e)              P<0.001 **       P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Interstitial Cell                                                                                                        | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|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   |                                                                                                             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/21/04                           EXPERIMENT: 99036 TEST: 01                                            Page 16      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -     TRANSGENIC MODEL EVALUATION II (PHEN
OLP                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Hyperplasia Atypical                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/14 (0%)        0/15 (0%)        1/15 (7%)        0/14 (0%)        1/15 (7%)        0/14 (0%)       | 
|POLY-3 RATE (b)    |        0/13.07          0/15.00          1/15.00          0/13.01          1/15.00          0/14.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             6.7%             0.0%             6.7%             0.0%            | 
|TERMINAL (d)       |        0/13 (0%)        0/15 (0%)        1/15 (7%)        0/13 (0%)        1/15 (7%)        0/14 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              183 (T)          ---              183 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.658N         (e)              P=0.529          (e)              P=0.529          (e)             | 
|POLY 3             |        P=0.653N         (e)              P=0.527          (e)              P=0.527          (e)             | 
|POLY 1.5           |        P=0.655N         (e)              P=0.524          (e)              P=0.524          (e)             | 
|POLY 6             |        P=0.653N         (e)              P=0.528          (e)              P=0.528          (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              P=0.529          (e)              P=0.529          (e)             | 
|COCH-ARM / FISHERS |        P=0.667N         (e)              P=0.517          (e)              P=0.517          (e)             | 
|ORDER RESTRICTED   |        P=0.512          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Hyperplasia Atypical                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        1/15 (7%)        0/15 (0%)        3/14 (21%)       5/15 (33%)      | 
|POLY-3 RATE (b)    |        0/15.00          0/13.00          1/14.00          0/15.00          3/13.00          5/15.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             7.1%             0.0%             23.1%            33.3%           | 
|TERMINAL (d)       |        0/15 (0%)        0/13 (0%)        1/14 (7%)        0/15 (0%)        3/13 (23%)       5/15 (33%)      | 
|FIRST INCIDENCE    |        ---              ---              184 (T)          ---              184 (T)          184 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              P=0.486          (e)              P=0.091          P=0.027 *       | 
|POLY 3             |        P<0.001 **       (e)              P=0.486          (e)              P=0.080          P=0.017 *       | 
|POLY 1.5           |        P<0.001 **       (e)              P=0.487          (e)              P=0.081          P=0.017 *       | 
|POLY 6             |        P<0.001 **       (e)              P=0.486          (e)              P=0.080          P=0.017 *       | 
|LOGISTIC REGRESSION|        (e)              (e)              P=0.486          (e)              P=0.091          P=0.027 *       | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              P=0.500          (e)              P=0.100          P=0.021 *       | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  04/21/04                           EXPERIMENT: 99036 TEST: 01                                            Page 17      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P16(INK4A)/(+/-) (C57BL/6))  -     TRANSGENIC MODEL EVALUATION II (PHEN
OLP                                                                                                                                 
                                         Terminal Sacrifice at 27 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|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 PPM            200 PPM          375 PPM          750 PPM          3000 PPM         12,000          | 
|                   |                                                                                             PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus: Endometrium                                                                                                              | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        15/15 (100%)     12/15 (80%)      14/15 (93%)      15/15 (100%)     13/15 (87%)      14/15 (93%)     | 
|POLY-3 RATE (b)    |        15/15.00         12/13.00         14/14.00         15/15.00         13/14.00         14/15.00        | 
|POLY-3 PERCENT (g) |        100.0%           92.3%            100.0%           100.0%           92.8%            93.3%           | 
|TERMINAL (d)       |        15/15 (100%)     12/13 (92%)      14/14 (100%)     15/15 (100%)     13/14 (93%)      14/15 (93%)     | 
|FIRST INCIDENCE    |        184 (T)          184 (T)          184 (T)          184 (T)          184 (T)          184 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.379N         P=0.471N         P=1.000N         (e)              P=0.486N         P=0.500N        | 
|POLY 3             |        P=0.372N         P=0.471N         P=1.000N         (e)              P=0.485N         P=0.500N        | 
|POLY 1.5           |        P=0.381N         P=0.448N         P=1.000N         (e)              P=0.465N         P=0.500N        | 
|POLY 6             |        P=0.371N         P=0.471N         P=1.000N         (e)              P=0.486N         P=0.500N        | 
|LOGISTIC REGRESSION|        P=0.378N         P=0.471N         P=1.000N         (e)              P=0.486N         P=0.500N        | 
|COCH-ARM / FISHERS |        P=0.659          P=0.112N         P=0.500N         (e)              P=0.241N         P=0.500N        | 
|ORDER RESTRICTED   |        P=0.265N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
(a)  Number of tumor-bearing animals /  number of animals examined at site.                                                         
                                                                                                                                   
(b)  Number of tumor-bearing animals / Poly-3 number                                                                                
(d)  Observed incidence at terminal kill.                                                                                           
(f)  Beneath the control incidence are the P-values associated with the trend                                                       
test.  Beneath the dosed group incidence are the P-values corresponding to                                                          
pairwise comparisons between the controls and that dosed group.  The life                                                           
table analysis regards tumors in animals dying prior to  terminal kill as                                                           
 being (directly or indirectly) the cause of death.                                                                                 
Logistic regression is an alternative                                                                                               
 method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage                                                       
and Fishers exact tests compare directly the overall incidence rates                                                                
For all tests a negative trend is indicated by N                                                                                    
(e)  Value of Statistic cannot be computed.                                                                                         
(g)  Poly-3 adjusted lifetime tumor incidence.                                                                                      
(I)  Interim sacrifice                                                                                                              
(T)  Terminal sacrifice                                                                                                             
#   Tumor rates based on number of animals necropsied.                                                                              
*   To the right of any statistical result, indicates significance at (P<=0.05).                                                    
**  To the right of any statistical result, indicates significance at (P<=0.01).                                                    
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.