https://ntp.niehs.nih.gov/go/12093

TDMS Study 99033-02 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: BIORELIANCE                               TRANSGENIC MODEL EVALUATION II (ASPARTAME)                      DATE: 03/05/03       
EXPERIMENT: 99033 TEST: 02                                                                                     TIME: 11:37:28       
TEST TYPE:  26-39 WEEKS                         CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-65406                              ROUTE: DOSED FEED                                              NTP C#: C99033       
PATHOLOGIST: LANNING, LYNDA                                                                                    CAS: 22839-47-0      
------------------------------------------------------------------------------------------------------------------------------------
                                                         FINAL #3/P53 MICE                                                          
               REASONS FOR REMOVAL:    ALL                                                                                          
               REMOVAL DATE RANGE:     ALL                                                                                          
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: BIORELIANCE                               TRANSGENIC MODEL EVALUATION II (ASPARTAME)                      DATE: 03/05/03       
EXPERIMENT: 99033 TEST: 02                                                                                     TIME: 11:37:28       
TEST TYPE:  26-39 WEEKS                         CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-65406                              ROUTE: DOSED FEED                                              NTP C#: C99033       
PATHOLOGIST: LANNING, LYNDA                                                                                    CAS: 22839-47-0      
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF       TRANSGENIC MODEL EVALUATION II (ASPA                                                                       
===============================================================                                                                     
Male Mice                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Adrenal Cortex                         Atrophy                                                                                      
Kidney                                 Nephropathy                                                                                  
Liver                                  Inflammation Chronic                                                                         
Liver: Hepatocyte, Periportal          Vacuolization Cytoplasmic Diffuse                                                            
Spleen                                 Atrophy                                                                                      
                                       Hematopoietic Cell Proliferation                                                             
Thymus                                 Atrophy Focal                                                                                
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Adrenal Cortex: Subcapsular            Hyperplasia Focal                                                                            
Lymph Node, Mandibular                 Hyperplasia                                                                                  
                                       Hyperplasia Lymphoid                                                                         
Thymus                                 Atrophy Focal                                                                                
===============================================================                                                                     
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions in        Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II 
(ASPA                                                                                                                               
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        14/15 (93%)      14/15 (93%)      12/15 (80%)      12/15 (80%)      10/15 (67%)      13/15 (87%)     | 
|POLY-3 RATE (b)    |        14/14.05         14/15.00         12/13.52         12/15.00         10/14.01         13/14.02        | 
|POLY-3 PERCENT (g) |        99.6%            93.3%            88.7%            80.0%            71.4%            92.7%           | 
|TERMINAL (d)       |        14/14 (100%)     14/15 (93%)      12/13 (92%)      12/15 (80%)      10/14 (71%)      13/14 (93%)     | 
|FIRST INCIDENCE    |        274 (T)          274 (T)          274 (T)          274 (T)          274 (T)          274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.321N         P=0.514N         P=0.485N         P=0.128N         P=0.056N         P=0.500N        | 
|POLY 3             |        P=0.352N         P=0.534N         P=0.321N         P=0.126N         P=0.047N*        P=0.513N        | 
|POLY 1.5           |        P=0.368N         P=0.599N         P=0.274N         P=0.151N         P=0.054N         P=0.535N        | 
|POLY 6             |        P=0.332N         P=0.515N         P=0.406N         P=0.119N         P=0.044N*        P=0.501N        | 
|LOGISTIC REGRESSION|        P=0.321N         P=0.514N         P=0.485N         P=0.128N         P=0.056N         P=0.500N        | 
|COCH-ARM / FISHERS |        P=0.312N         P=0.759N         P=0.299N         P=0.299N         P=0.084N         P=0.500N        | 
|ORDER RESTRICTED   |        P=0.110N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/14.00          0/14.05          0/14.00          0/15.00          0/15.00          0/15.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/14 (0%)        0/14 (0%)        0/14 (0%)        0/15 (0%)        0/15 (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:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 2       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        1/15 (7%)        3/15 (20%)       2/15 (13%)       1/15 (7%)        3/15 (20%)      | 
|POLY-3 RATE (b)    |        0/14.05          1/15.00          3/13.52          2/15.00          1/14.01          3/14.02         | 
|POLY-3 PERCENT (g) |        0.0%             6.7%             22.2%            13.3%            7.1%             21.4%           | 
|TERMINAL (d)       |        0/14 (0%)        1/15 (7%)        3/13 (23%)       2/15 (13%)       1/14 (7%)        3/14 (21%)      | 
|FIRST INCIDENCE    |        ---              274 (T)          274 (T)          274 (T)          274 (T)          274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.170          P=0.514          P=0.102          P=0.251          P=0.500          P=0.115         | 
|POLY 3             |        P=0.164          P=0.513          P=0.098          P=0.247          P=0.499          P=0.105         | 
|POLY 1.5           |        P=0.164          P=0.511          P=0.101          P=0.244          P=0.498          P=0.104         | 
|POLY 6             |        P=0.164          P=0.514          P=0.094          P=0.248          P=0.500          P=0.105         | 
|LOGISTIC REGRESSION|        (e)              P=0.514          P=0.102          P=0.251          P=0.500          P=0.115         | 
|COCH-ARM / FISHERS |        P=0.174          P=0.500          P=0.112          P=0.241          P=0.500          P=0.112         | 
|ORDER RESTRICTED   |        P=0.062          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/14.00          0/14.05          0/14.00          0/15.00          0/15.00          0/15.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/14 (0%)        0/14 (0%)        0/14 (0%)        0/15 (0%)        0/15 (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:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 3       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex: Subcapsular                                                                                                      | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        0/15 (0%)        2/15 (13%)       1/15 (7%)        2/15 (13%)       1/15 (7%)       | 
|POLY-3 RATE (b)    |        1/14.05          0/15.00          2/13.52          1/15.00          2/14.01          1/14.02         | 
|POLY-3 PERCENT (g) |        7.1%             0.0%             14.8%            6.7%             14.3%            7.1%            | 
|TERMINAL (d)       |        1/14 (7%)        0/15 (0%)        2/13 (15%)       1/15 (7%)        2/14 (14%)       1/14 (7%)       | 
|FIRST INCIDENCE    |        274 (T)          ---              274 (T)          274 (T)          274 (T)          274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.500          P=0.486N         P=0.473          P=0.749N         P=0.500          P=0.764         | 
|POLY 3             |        P=0.483          P=0.487N         P=0.486          P=0.746N         P=0.499          P=0.760         | 
|POLY 1.5           |        P=0.485          P=0.489N         P=0.493          P=0.749N         P=0.496          P=0.759         | 
|POLY 6             |        P=0.483          P=0.486N         P=0.479          P=0.745N         P=0.500          P=0.761         | 
|LOGISTIC REGRESSION|        P=0.500          (e)              P=0.473          P=0.749N         P=0.500          P=0.764         | 
|COCH-ARM / FISHERS |        P=0.505          P=0.500N         P=0.500          P=0.759N         P=0.500          P=0.759N        | 
|ORDER RESTRICTED   |        P=0.451          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex: Subcapsular                                                                                                      | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        12/15 (80%)      13/15 (87%)      13/14 (93%)      15/15 (100%)     15/15 (100%)     15/15 (100%)    | 
|POLY-3 RATE (b)    |        12/14.00         13/14.05         13/14.00         15/15.00         15/15.00         15/15.00        | 
|POLY-3 PERCENT (g) |        85.7%            92.6%            92.9%            100.0%           100.0%           100.0%          | 
|TERMINAL (d)       |        12/14 (86%)      13/14 (93%)      13/14 (93%)      15/15 (100%)     15/15 (100%)     15/15 (100%)    | 
|FIRST INCIDENCE    |        275 (T)          275 (T)          275 (T)          275 (T)          275 (T)          275 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.095          P=0.500          P=0.500          P=0.221          P=0.221          P=0.221         | 
|POLY 3             |        P=0.096          P=0.509          P=0.500          P=0.215          P=0.215          P=0.215         | 
|POLY 1.5           |        P=0.083          P=0.534          P=0.490          P=0.206          P=0.206          P=0.206         | 
|POLY 6             |        P=0.099          P=0.500          P=0.500          P=0.216          P=0.216          P=0.216         | 
|LOGISTIC REGRESSION|        P=0.095          P=0.500          P=0.250          P=0.221          P=0.221          P=0.221         | 
|COCH-ARM / FISHERS |        P=0.037 *        P=0.500          P=0.326          P=0.112          P=0.112          P=0.112         | 
|ORDER RESTRICTED   |        P=0.050          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 4       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Infiltration Cellular Focal Lymphocyte                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/15 (33%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         1/15 (7%)       | 
|POLY-3 RATE (b)    |        5/14.05          0/0.00           0/0.00           0/0.00           0/0.00           1/14.02         | 
|POLY-3 PERCENT (g) |        35.6%            0.0%             0.0%             0.0%             0.0%             7.1%            | 
|TERMINAL (d)       |        5/14 (36%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         1/14 (7%)       | 
|FIRST INCIDENCE    |        274 (T)          ---              ---              ---              ---              274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.057N         P=1.000          P=1.000N         P=1.000          P=1.000N         P=0.087N        | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              P=0.079N        | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              P=0.080N        | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              P=0.078N        | 
|LOGISTIC REGRESSION|        P=0.057N         (e)              (e)              (e)              (e)              P=0.087N        | 
|COCH-ARM / FISHERS |        P=0.055N         P=1.000          P=1.000          P=1.000          P=1.000          P=0.084N        | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Harderian Gland                                                                                                                  | 
|     Infiltration Cellular Focal Lymphocyte                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         3/15 (20%)      | 
|POLY-3 RATE (b)    |        1/14.00          0/0.00           0/0.00           0/0.00           0/0.00           3/15.00         | 
|POLY-3 PERCENT (g) |        7.1%             0.0%             0.0%             0.0%             0.0%             20.0%           | 
|TERMINAL (d)       |        1/14 (7%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         3/15 (20%)      | 
|FIRST INCIDENCE    |        275 (T)          ---              ---              ---              ---              275 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.235          P=1.000          P=1.000N         P=1.000N         P=1.000          P=0.324         | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              P=0.324         | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              P=0.323         | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              P=0.324         | 
|LOGISTIC REGRESSION|        P=0.235          (e)              (e)              (e)              (e)              P=0.324         | 
|COCH-ARM / FISHERS |        P=0.210          P=1.000          P=1.000          P=1.000          P=1.000          P=0.299         | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 5       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/14 (29%)       0/15 (0%)        0/15 (0%)        0/15 (0%)        0/14 (0%)        3/15 (20%)      | 
|POLY-3 RATE (b)    |        4/14.00          0/15.00          0/13.52          0/15.00          0/14.00          3/14.02         | 
|POLY-3 PERCENT (g) |        28.6%            0.0%             0.0%             0.0%             0.0%             21.4%           | 
|TERMINAL (d)       |        4/14 (29%)       0/15 (0%)        0/13 (0%)        0/15 (0%)        0/14 (0%)        3/14 (21%)      | 
|FIRST INCIDENCE    |        274 (T)          ---              ---              ---              ---              274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.283          P=0.048N*        P=0.065N         P=0.048N*        P=0.056N         P=0.500N        | 
|POLY 3             |        P=0.292          P=0.037N*        P=0.048N*        P=0.037N*        P=0.044N*        P=0.499N        | 
|POLY 1.5           |        P=0.287          P=0.037N*        P=0.044N*        P=0.037N*        P=0.044N*        P=0.494N        | 
|POLY 6             |        P=0.295          P=0.037N*        P=0.051N         P=0.037N*        P=0.044N*        P=0.500N        | 
|LOGISTIC REGRESSION|        P=0.283          (e)              (e)              (e)              (e)              P=0.500N        | 
|COCH-ARM / FISHERS |        P=0.292          P=0.042N*        P=0.042N*        P=0.042N*        P=0.049N*        P=0.458N        | 
|ORDER RESTRICTED   |        P=0.009N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|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)    |        0/14.00          0/14.00          0/14.23          0/15.00          0/15.00          0/15.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/14 (0%)        0/14 (0%)        0/14 (0%)        0/15 (0%)        0/15 (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:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 6       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Dilatation Diffuse                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/14 (0%)        2/15 (13%)       0/15 (0%)        1/15 (7%)        0/14 (0%)        1/15 (7%)       | 
|POLY-3 RATE (b)    |        0/14.00          2/15.00          0/13.52          1/15.00          0/14.00          1/14.02         | 
|POLY-3 PERCENT (g) |        0.0%             13.3%            0.0%             6.7%             0.0%             7.1%            | 
|TERMINAL (d)       |        0/14 (0%)        2/15 (13%)       0/13 (0%)        1/15 (7%)        0/14 (0%)        1/14 (7%)       | 
|FIRST INCIDENCE    |        ---              274 (T)          ---              274 (T)          ---              274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.594          P=0.251          (e)              P=0.514          (e)              P=0.500         | 
|POLY 3             |        P=0.599          P=0.247          (e)              P=0.514          (e)              P=0.500         | 
|POLY 1.5           |        P=0.596          P=0.247          (e)              P=0.514          (e)              P=0.502         | 
|POLY 6             |        P=0.601          P=0.247          (e)              P=0.514          (e)              P=0.500         | 
|LOGISTIC REGRESSION|        (e)              P=0.251          (e)              P=0.514          (e)              P=0.500         | 
|COCH-ARM / FISHERS |        P=0.602          P=0.259          (e)              P=0.517          (e)              P=0.517         | 
|ORDER RESTRICTED   |        P=0.340          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Dilatation Diffuse                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        2/14 (14%)       3/15 (20%)       0/15 (0%)        0/15 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        1/14.00          2/14.00          3/14.23          0/15.00          0/15.00          0/15.00         | 
|POLY-3 PERCENT (g) |        7.1%             14.3%            21.1%            0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        1/14 (7%)        2/14 (14%)       3/14 (21%)       0/15 (0%)        0/15 (0%)        0/15 (0%)       | 
|FIRST INCIDENCE    |        275 (T)          275 (T)          275 (T)          ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.065N         P=0.500          P=0.298          P=0.486N         P=0.486N         P=0.486N        | 
|POLY 3             |        P=0.061N         P=0.500          P=0.303          P=0.486N         P=0.486N         P=0.486N        | 
|POLY 1.5           |        P=0.061N         P=0.499          P=0.309          P=0.487N         P=0.487N         P=0.487N        | 
|POLY 6             |        P=0.062N         P=0.500          P=0.299          P=0.486N         P=0.486N         P=0.486N        | 
|LOGISTIC REGRESSION|        P=0.065N         P=0.500          P=0.298          (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.069N         P=0.473          P=0.299          P=0.500N         P=0.500N         P=0.500N        | 
|ORDER RESTRICTED   |        P=0.099N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 7       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Dilatation Focal                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/14 (0%)        2/15 (13%)       0/15 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/14.00          2/15.00          0/13.52          0/15.00          0/14.00          0/14.02         | 
|POLY-3 PERCENT (g) |        0.0%             13.3%            0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/14 (0%)        2/15 (13%)       0/13 (0%)        0/15 (0%)        0/14 (0%)        0/14 (0%)       | 
|FIRST INCIDENCE    |        ---              274 (T)          ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.289N         P=0.251          (e)              (e)              (e)              (e)             | 
|POLY 3             |        P=0.266N         P=0.247          (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        P=0.270N         P=0.247          (e)              (e)              (e)              (e)             | 
|POLY 6             |        P=0.264N         P=0.247          (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              P=0.251          (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.285N         P=0.259          (e)              (e)              (e)              (e)             | 
|ORDER RESTRICTED   |        P=0.190N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Dilatation Focal                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        6/15 (40%)       5/14 (36%)       2/15 (13%)       5/15 (33%)       4/15 (27%)       4/15 (27%)      | 
|POLY-3 RATE (b)    |        6/14.00          5/14.00          2/14.23          5/15.00          4/15.00          4/15.00         | 
|POLY-3 PERCENT (g) |        42.9%            35.7%            14.1%            33.3%            26.7%            26.7%           | 
|TERMINAL (d)       |        6/14 (43%)       5/14 (36%)       2/14 (14%)       5/15 (33%)       4/15 (27%)       4/15 (27%)      | 
|FIRST INCIDENCE    |        275 (T)          275 (T)          275 (T)          275 (T)          275 (T)          275 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.351N         P=0.500N         P=0.109N         P=0.443N         P=0.303N         P=0.303N        | 
|POLY 3             |        P=0.358N         P=0.500N         P=0.096N         P=0.444N         P=0.304N         P=0.304N        | 
|POLY 1.5           |        P=0.365N         P=0.503N         P=0.092N         P=0.447N         P=0.306N         P=0.306N        | 
|POLY 6             |        P=0.354N         P=0.500N         P=0.100N         P=0.444N         P=0.303N         P=0.303N        | 
|LOGISTIC REGRESSION|        P=0.351N         P=0.500N         P=0.109N         P=0.443N         P=0.303N         P=0.303N        | 
|COCH-ARM / FISHERS |        P=0.391N         P=0.558N         P=0.107N         P=0.500N         P=0.350N         P=0.350N        | 
|ORDER RESTRICTED   |        P=0.278N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 8       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Infiltration Cellular Focal Lymphocyte                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/15 (13%)       2/15 (13%)       4/15 (27%)       1/15 (7%)        2/14 (14%)       5/15 (33%)      | 
|POLY-3 RATE (b)    |        2/14.05          2/15.00          4/13.52          1/15.00          2/14.00          5/14.02         | 
|POLY-3 PERCENT (g) |        14.2%            13.3%            29.6%            6.7%             14.3%            35.7%           | 
|TERMINAL (d)       |        2/14 (14%)       2/15 (13%)       4/13 (31%)       1/15 (7%)        2/14 (14%)       5/14 (36%)      | 
|FIRST INCIDENCE    |        274 (T)          274 (T)          274 (T)          274 (T)          274 (T)          274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.115          P=0.676N         P=0.289          P=0.475N         P=0.702          P=0.196         | 
|POLY 3             |        P=0.110          P=0.674N         P=0.306          P=0.477N         P=0.698          P=0.192         | 
|POLY 1.5           |        P=0.111          P=0.679N         P=0.315          P=0.481N         P=0.693          P=0.190         | 
|POLY 6             |        P=0.111          P=0.673N         P=0.297          P=0.476N         P=0.699          P=0.193         | 
|LOGISTIC REGRESSION|        P=0.115          P=0.676N         P=0.289          P=0.475N         P=0.702          P=0.196         | 
|COCH-ARM / FISHERS |        P=0.116          P=0.701N         P=0.326          P=0.500N         P=0.674          P=0.195         | 
|ORDER RESTRICTED   |        P=0.114          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Infiltration Cellular Focal Lymphocyte                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/15 (27%)       3/15 (20%)       4/15 (27%)       6/15 (40%)       4/15 (27%)       4/15 (27%)      | 
|POLY-3 RATE (b)    |        4/14.00          3/14.05          4/14.23          6/15.00          4/15.00          4/15.00         | 
|POLY-3 PERCENT (g) |        28.6%            21.4%            28.1%            40.0%            26.7%            26.7%           | 
|TERMINAL (d)       |        4/14 (29%)       3/14 (21%)       4/14 (29%)       6/15 (40%)       4/15 (27%)       4/15 (27%)      | 
|FIRST INCIDENCE    |        275 (T)          275 (T)          275 (T)          275 (T)          275 (T)          275 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.538N         P=0.500N         P=0.659          P=0.401          P=0.616N         P=0.616N        | 
|POLY 3             |        P=0.538N         P=0.498N         P=0.647N         P=0.402          P=0.614N         P=0.614N        | 
|POLY 1.5           |        P=0.547N         P=0.493N         P=0.639N         P=0.399          P=0.616N         P=0.616N        | 
|POLY 6             |        P=0.534N         P=0.500N         P=0.655N         P=0.402          P=0.614N         P=0.614N        | 
|LOGISTIC REGRESSION|        P=0.538N         P=0.500N         P=0.659          P=0.401          P=0.616N         P=0.616N        | 
|COCH-ARM / FISHERS |        P=0.537          P=0.500N         P=0.659N         P=0.350          P=0.659N         P=0.659N        | 
|ORDER RESTRICTED   |        P=0.646          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 9       
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/15 (27%)       0/15 (0%)        0/15 (0%)        0/15 (0%)        0/14 (0%)        1/15 (7%)       | 
|POLY-3 RATE (b)    |        4/15.00          0/15.00          0/13.52          0/15.00          0/14.00          1/14.02         | 
|POLY-3 PERCENT (g) |        26.7%            0.0%             0.0%             0.0%             0.0%             7.1%            | 
|TERMINAL (d)       |        3/14 (21%)       0/15 (0%)        0/13 (0%)        0/15 (0%)        0/14 (0%)        1/14 (7%)       | 
|FIRST INCIDENCE    |        102              ---              ---              ---              ---              274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.321N         P=0.055N         P=0.068N         P=0.055N         P=0.064N         P=0.179N        | 
|POLY 3             |        P=0.286N         P=0.045N*        P=0.058N         P=0.045N*        P=0.053N         P=0.184N        | 
|POLY 1.5           |        P=0.291N         P=0.045N*        P=0.054N         P=0.045N*        P=0.053N         P=0.182N        | 
|POLY 6             |        P=0.282N         P=0.045N*        P=0.062N         P=0.045N*        P=0.053N         P=0.185N        | 
|LOGISTIC REGRESSION|        P=0.278N         (e)              P=0.043N*        (e)              (e)              P=0.150N        | 
|COCH-ARM / FISHERS |        P=0.318N         P=0.050N         P=0.050N         P=0.050N         P=0.057N         P=0.165N        | 
|ORDER RESTRICTED   |        P<0.001N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|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)    |        0/14.00          0/14.05          0/14.23          0/15.00          0/15.00          0/15.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/14 (0%)        0/14 (0%)        0/14 (0%)        0/15 (0%)        0/15 (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:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 10      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Necrosis Focal                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/15 (13%)       1/15 (7%)        0/15 (0%)        0/15 (0%)        0/14 (0%)        1/15 (7%)       | 
|POLY-3 RATE (b)    |        2/14.05          1/15.00          0/13.52          0/15.00          0/14.00          1/14.02         | 
|POLY-3 PERCENT (g) |        14.2%            6.7%             0.0%             0.0%             0.0%             7.1%            | 
|TERMINAL (d)       |        2/14 (14%)       1/15 (7%)        0/13 (0%)        0/15 (0%)        0/14 (0%)        1/14 (7%)       | 
|FIRST INCIDENCE    |        274 (T)          274 (T)          ---              ---              ---              274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.516N         P=0.475N         P=0.252N         P=0.221N         P=0.236N         P=0.500N        | 
|POLY 3             |        P=0.506N         P=0.477N         P=0.240N         P=0.216N         P=0.232N         P=0.501N        | 
|POLY 1.5           |        P=0.509N         P=0.481N         P=0.236N         P=0.219N         P=0.235N         P=0.502N        | 
|POLY 6             |        P=0.503N         P=0.476N         P=0.244N         P=0.216N         P=0.231N         P=0.500N        | 
|LOGISTIC REGRESSION|        P=0.516N         P=0.475N         (e)              (e)              (e)              P=0.500N        | 
|COCH-ARM / FISHERS |        P=0.517N         P=0.500N         P=0.241N         P=0.241N         P=0.259N         P=0.500N        | 
|ORDER RESTRICTED   |        P=0.098N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Necrosis Focal                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        1/15 (7%)       | 
|POLY-3 RATE (b)    |        0/14.00          0/14.05          0/14.23          0/15.00          0/15.00          1/15.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             6.7%            | 
|TERMINAL (d)       |        0/14 (0%)        0/14 (0%)        0/14 (0%)        0/15 (0%)        0/15 (0%)        1/15 (7%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              275 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.113          (e)              (e)              (e)              (e)              P=0.514         | 
|POLY 3             |        P=0.111          (e)              (e)              (e)              (e)              P=0.514         | 
|POLY 1.5           |        P=0.110          (e)              (e)              (e)              (e)              P=0.513         | 
|POLY 6             |        P=0.112          (e)              (e)              (e)              (e)              P=0.514         | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              P=0.514         | 
|COCH-ARM / FISHERS |        P=0.105          (e)              (e)              (e)              (e)              P=0.500         | 
|ORDER RESTRICTED   |        P=0.074          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 11      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Necrosis Focal                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/14.05          0/15.00          0/13.52          0/15.00          0/14.00          0/14.02         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/14 (0%)        0/15 (0%)        0/13 (0%)        0/15 (0%)        0/14 (0%)        0/14 (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               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Necrosis Focal                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        2/15 (13%)       0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/14.00          0/14.05          0/14.23          0/15.00          2/15.00          0/15.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             13.3%            0.0%            | 
|TERMINAL (d)       |        0/14 (0%)        0/14 (0%)        0/14 (0%)        0/15 (0%)        2/15 (13%)       0/15 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              275 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.430          (e)              (e)              (e)              P=0.251          (e)             | 
|POLY 3             |        P=0.438          (e)              (e)              (e)              P=0.248          (e)             | 
|POLY 1.5           |        P=0.434          (e)              (e)              (e)              P=0.247          (e)             | 
|POLY 6             |        P=0.440          (e)              (e)              (e)              P=0.248          (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              P=0.251          (e)             | 
|COCH-ARM / FISHERS |        P=0.414          (e)              (e)              (e)              P=0.241          (e)             | 
|ORDER RESTRICTED   |        P=0.190          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 12      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte, Periportal                                                                                                    | 
|     Vacuolization Cytoplasmic Diffuse                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/15 (13%)       0/15 (0%)        0/15 (0%)        0/15 (0%)        0/14 (0%)        4/15 (27%)      | 
|POLY-3 RATE (b)    |        2/14.05          0/15.00          0/13.52          0/15.00          0/14.00          4/14.02         | 
|POLY-3 PERCENT (g) |        14.2%            0.0%             0.0%             0.0%             0.0%             28.5%           | 
|TERMINAL (d)       |        2/14 (14%)       0/15 (0%)        0/13 (0%)        0/15 (0%)        0/14 (0%)        4/14 (29%)      | 
|FIRST INCIDENCE    |        274 (T)          ---              ---              ---              ---              274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.012 *        P=0.221N         P=0.252N         P=0.221N         P=0.236N         P=0.326         | 
|POLY 3             |        P=0.009 **       P=0.216N         P=0.240N         P=0.216N         P=0.232N         P=0.325         | 
|POLY 1.5           |        P=0.009 **       P=0.219N         P=0.236N         P=0.219N         P=0.235N         P=0.323         | 
|POLY 6             |        P=0.009 **       P=0.216N         P=0.244N         P=0.216N         P=0.231N         P=0.326         | 
|LOGISTIC REGRESSION|        P=0.012 *        (e)              (e)              (e)              (e)              P=0.326         | 
|COCH-ARM / FISHERS |        P=0.013 *        P=0.241N         P=0.241N         P=0.241N         P=0.259N         P=0.326         | 
|ORDER RESTRICTED   |        P=0.003 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte, Periportal                                                                                                    | 
|     Vacuolization Cytoplasmic Diffuse                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|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)    |        0/14.00          0/14.05          0/14.23          0/15.00          0/15.00          0/15.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/14 (0%)        0/14 (0%)        0/14 (0%)        0/15 (0%)        0/15 (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:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 13      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Perivascular                                                                                                               | 
|     Infiltration Cellular Lymphocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        2/14 (14%)       0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/14.05          0/15.00          0/13.52          0/15.00          2/14.00          0/14.02         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             14.3%            0.0%            | 
|TERMINAL (d)       |        0/14 (0%)        0/15 (0%)        0/13 (0%)        0/15 (0%)        2/14 (14%)       0/14 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              274 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.412          (e)              (e)              (e)              P=0.236          (e)             | 
|POLY 3             |        P=0.380          (e)              (e)              (e)              P=0.230          (e)             | 
|POLY 1.5           |        P=0.381          (e)              (e)              (e)              P=0.227          (e)             | 
|POLY 6             |        P=0.382          (e)              (e)              (e)              P=0.231          (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              P=0.236          (e)             | 
|COCH-ARM / FISHERS |        P=0.411          (e)              (e)              (e)              P=0.224          (e)             | 
|ORDER RESTRICTED   |        P=0.173          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Perivascular                                                                                                               | 
|     Infiltration Cellular Lymphocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/14.00          0/14.05          0/14.00          0/15.00          0/15.00          0/15.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/14 (0%)        0/14 (0%)        0/14 (0%)        0/15 (0%)        0/15 (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:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 14      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/14 (7%)        3/15 (20%)       0/14 (0%)        2/15 (13%)       0/14 (0%)        2/15 (13%)      | 
|POLY-3 RATE (b)    |        1/14.00          3/15.00          0/12.52          2/15.00          0/14.00          2/14.02         | 
|POLY-3 PERCENT (g) |        7.1%             20.0%            0.0%             13.3%            0.0%             14.3%           | 
|TERMINAL (d)       |        1/14 (7%)        3/15 (20%)       0/12 (0%)        2/15 (13%)       0/14 (0%)        2/14 (14%)      | 
|FIRST INCIDENCE    |        274 (T)          274 (T)          ---              274 (T)          ---              274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.565          P=0.324          P=0.531N         P=0.525          P=0.500N         P=0.500         | 
|POLY 3             |        P=0.578          P=0.324          P=0.522N         P=0.524          P=0.500N         P=0.500         | 
|POLY 1.5           |        P=0.574          P=0.324          P=0.516N         P=0.524          P=0.500N         P=0.503         | 
|POLY 6             |        P=0.582          P=0.324          P=0.527N         P=0.524          P=0.500N         P=0.500         | 
|LOGISTIC REGRESSION|        P=0.565          P=0.324          (e)              P=0.525          (e)              P=0.500         | 
|COCH-ARM / FISHERS |        P=0.575          P=0.326          P=0.500N         P=0.527          P=0.500N         P=0.527         | 
|ORDER RESTRICTED   |        P=0.477          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        3/15 (20%)       2/13 (15%)       0/13 (0%)        1/15 (7%)        1/15 (7%)        0/14 (0%)       | 
|POLY-3 RATE (b)    |        3/14.00          2/13.00          0/12.23          1/15.00          1/15.00          0/14.00         | 
|POLY-3 PERCENT (g) |        21.4%            15.4%            0.0%             6.7%             6.7%             0.0%            | 
|TERMINAL (d)       |        3/14 (21%)       2/13 (15%)       0/12 (0%)        1/15 (7%)        1/15 (7%)        0/14 (0%)       | 
|FIRST INCIDENCE    |        275 (T)          275 (T)          ---              275 (T)          275 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.085N         P=0.536N         P=0.143N         P=0.273N         P=0.273N         P=0.115N        | 
|POLY 3             |        P=0.085N         P=0.535N         P=0.130N         P=0.273N         P=0.273N         P=0.105N        | 
|POLY 1.5           |        P=0.087N         P=0.537N         P=0.126N         P=0.274N         P=0.274N         P=0.106N        | 
|POLY 6             |        P=0.084N         P=0.535N         P=0.133N         P=0.273N         P=0.273N         P=0.105N        | 
|LOGISTIC REGRESSION|        P=0.085N         P=0.536N         (e)              P=0.273N         P=0.273N         (e)             | 
|COCH-ARM / FISHERS |        P=0.091N         P=0.572N         P=0.139N         P=0.299N         P=0.299N         P=0.125N        | 
|ORDER RESTRICTED   |        P=0.028N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 15      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/14 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/14.00          0/15.00          0/12.52          0/15.00          0/14.00          0/14.02         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/14 (0%)        0/15 (0%)        0/12 (0%)        0/15 (0%)        0/14 (0%)        0/14 (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               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Hyperplasia Lymphoid                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/15 (13%)       0/13 (0%)        0/13 (0%)        0/15 (0%)        0/15 (0%)        0/14 (0%)       | 
|POLY-3 RATE (b)    |        2/15.00          0/13.00          0/12.23          0/15.00          0/15.00          0/14.00         | 
|POLY-3 PERCENT (g) |        13.3%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        1/14 (7%)        0/13 (0%)        0/12 (0%)        0/15 (0%)        0/15 (0%)        0/14 (0%)       | 
|FIRST INCIDENCE    |        36               ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.201N         P=0.256N         P=0.257N         P=0.232N         P=0.232N         P=0.240N        | 
|POLY 3             |        P=0.190N         P=0.265N         P=0.280N         P=0.232N         P=0.232N         P=0.247N        | 
|POLY 1.5           |        P=0.191N         P=0.265N         P=0.275N         P=0.232N         P=0.232N         P=0.247N        | 
|POLY 6             |        P=0.189N         P=0.265N         P=0.283N         P=0.232N         P=0.232N         P=0.247N        | 
|LOGISTIC REGRESSION|        P=0.413N         (e)              P=0.378N         (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.200N         P=0.278N         P=0.278N         P=0.241N         P=0.241N         P=0.259N        | 
|ORDER RESTRICTED   |        P=0.010N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 16      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Intermedia                                                                                                 | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/13 (0%)        0/13 (0%)        0/11 (0%)        0/8 (0%)         0/10 (0%)        0/12 (0%)       | 
|POLY-3 RATE (b)    |        0/13.00          0/13.00          0/10.07          0/8.00           0/10.00          0/12.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/13 (0%)        0/13 (0%)        0/10 (0%)        0/8 (0%)         0/10 (0%)        0/12 (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               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pituitary Gland: Pars Intermedia                                                                                                 | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/9 (0%)         0/14 (0%)        1/13 (8%)        0/14 (0%)        2/11 (18%)       2/14 (14%)      | 
|POLY-3 RATE (b)    |        0/9.00           0/14.00          1/13.00          0/14.00          2/11.00          2/14.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             7.7%             0.0%             18.2%            14.3%           | 
|TERMINAL (d)       |        0/9 (0%)         0/14 (0%)        1/13 (8%)        0/14 (0%)        2/11 (18%)       2/14 (14%)      | 
|FIRST INCIDENCE    |        ---              ---              275 (T)          ---              275 (T)          275 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.062          (e)              P=0.573          (e)              P=0.280          P=0.338         | 
|POLY 3             |        P=0.060          (e)              P=0.573          (e)              P=0.275          P=0.336         | 
|POLY 1.5           |        P=0.060          (e)              P=0.573          (e)              P=0.275          P=0.336         | 
|POLY 6             |        P=0.060          (e)              P=0.573          (e)              P=0.275          P=0.336         | 
|LOGISTIC REGRESSION|        (e)              (e)              P=0.573          (e)              P=0.280          P=0.338         | 
|COCH-ARM / FISHERS |        P=0.060          (e)              P=0.591          (e)              P=0.289          P=0.360         | 
|ORDER RESTRICTED   |        P=0.141          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 17      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Salivary Glands                                                                                                                  | 
|     Infiltration Cellular Focal Lymphocyte                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        9/15 (60%)       1/1 (100%)       0/1 (0%)         0/0 (0%)         1/1 (100%)       10/15 (67%)     | 
|POLY-3 RATE (b)    |        9/14.05          1/1.00           0/0.45           0/0.00           1/1.00           10/14.02        | 
|POLY-3 PERCENT (g) |        64.1%            100.0%           0.0%             0.0%             100.0%           71.3%           | 
|TERMINAL (d)       |        9/14 (64%)       1/1 (100%)       0/0 (0%)         0/0 (0%)         1/1 (100%)       10/14 (71%)     | 
|FIRST INCIDENCE    |        274 (T)          274 (T)          ---              ---              274 (T)          274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.462          P=0.638          P=1.000          P=1.000          P=0.638          P=0.500         | 
|POLY 3             |        (e)              P=0.638          P=0.681N         (e)              P=0.638          P=0.496         | 
|POLY 1.5           |        (e)              P=0.632          P=0.580N         (e)              P=0.632          P=0.490         | 
|POLY 6             |        (e)              P=0.640          P=0.784N         (e)              P=0.640          P=0.500         | 
|LOGISTIC REGRESSION|        P=0.462          P=0.638          (e)              (e)              P=0.638          P=0.500         | 
|COCH-ARM / FISHERS |        P=0.403          P=0.625          P=0.438N         P=1.000          P=0.625          P=0.500         | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Salivary Glands                                                                                                                  | 
|     Infiltration Cellular Focal Lymphocyte                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        6/15 (40%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         8/15 (53%)      | 
|POLY-3 RATE (b)    |        6/14.00          0/0.00           0/0.00           0/0.00           0/0.00           8/15.00         | 
|POLY-3 PERCENT (g) |        42.9%            0.0%             0.0%             0.0%             0.0%             53.3%           | 
|TERMINAL (d)       |        6/14 (43%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         8/15 (53%)      | 
|FIRST INCIDENCE    |        275 (T)          ---              ---              ---              ---              275 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.355          P=1.000          P=1.000          P=1.000          P=1.000          P=0.425         | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              P=0.426         | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              P=0.423         | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              P=0.426         | 
|LOGISTIC REGRESSION|        P=0.355          (e)              (e)              (e)              (e)              P=0.425         | 
|COCH-ARM / FISHERS |        P=0.292          P=1.000          P=1.000          P=1.000          P=1.000          P=0.358         | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 18      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/15 (13%)       0/15 (0%)        0/15 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        2/14.05          0/15.00          0/13.52          0/15.00          0/14.00          0/14.02         | 
|POLY-3 PERCENT (g) |        14.2%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        2/14 (14%)       0/15 (0%)        0/13 (0%)        0/15 (0%)        0/14 (0%)        0/14 (0%)       | 
|FIRST INCIDENCE    |        274 (T)          ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.207N         P=0.221N         P=0.252N         P=0.221N         P=0.236N         P=0.236N        | 
|POLY 3             |        P=0.201N         P=0.216N         P=0.240N         P=0.216N         P=0.232N         P=0.231N        | 
|POLY 1.5           |        P=0.202N         P=0.219N         P=0.236N         P=0.219N         P=0.235N         P=0.233N        | 
|POLY 6             |        P=0.200N         P=0.216N         P=0.244N         P=0.216N         P=0.231N         P=0.231N        | 
|LOGISTIC REGRESSION|        P=0.207N         (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.208N         P=0.241N         P=0.241N         P=0.241N         P=0.259N         P=0.241N        | 
|ORDER RESTRICTED   |        P=0.008N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|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)    |        0/14.00          0/14.05          0/14.23          0/15.00          0/15.00          0/15.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/14 (0%)        0/14 (0%)        0/14 (0%)        0/15 (0%)        0/15 (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:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 19      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)        1/14 (7%)        2/15 (13%)      | 
|POLY-3 RATE (b)    |        0/14.05          0/15.00          0/13.52          0/15.00          1/14.00          2/15.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             7.1%             13.3%           | 
|TERMINAL (d)       |        0/14 (0%)        0/15 (0%)        0/13 (0%)        0/15 (0%)        1/14 (7%)        1/14 (7%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              274 (T)          71              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.015 *        (e)              (e)              (e)              P=0.500          P=0.240         | 
|POLY 3             |        P=0.015 *        (e)              (e)              (e)              P=0.499          P=0.247         | 
|POLY 1.5           |        P=0.015 *        (e)              (e)              (e)              P=0.497          P=0.244         | 
|POLY 6             |        P=0.015 *        (e)              (e)              (e)              P=0.500          P=0.248         | 
|LOGISTIC REGRESSION|        P=0.026 *        (e)              (e)              (e)              P=0.500          P=0.233         | 
|COCH-ARM / FISHERS |        P=0.014 *        (e)              (e)              (e)              P=0.483          P=0.241         | 
|ORDER RESTRICTED   |        P=0.034 *        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        3/15 (20%)       4/15 (27%)       1/15 (7%)        3/15 (20%)       1/15 (7%)        1/15 (7%)       | 
|POLY-3 RATE (b)    |        3/15.00          4/14.05          1/14.23          3/15.00          1/15.00          1/15.00         | 
|POLY-3 PERCENT (g) |        20.0%            28.5%            7.0%             20.0%            6.7%             6.7%            | 
|TERMINAL (d)       |        2/14 (14%)       4/14 (29%)       1/14 (7%)        3/15 (20%)       1/15 (7%)        1/15 (7%)       | 
|FIRST INCIDENCE    |        36               275 (T)          275 (T)          275 (T)          275 (T)          275 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.110N         P=0.500          P=0.303N         P=0.641N         P=0.285N         P=0.285N        | 
|POLY 3             |        P=0.116N         P=0.461          P=0.318N         P=0.670          P=0.298N         P=0.298N        | 
|POLY 1.5           |        P=0.119N         P=0.468          P=0.311N         P=0.670          P=0.298N         P=0.298N        | 
|POLY 6             |        P=0.115N         P=0.460          P=0.323N         P=0.670          P=0.298N         P=0.298N        | 
|LOGISTIC REGRESSION|        P=0.163N         P=0.479          P=0.374N         P=0.641N         P=0.285N         P=0.285N        | 
|COCH-ARM / FISHERS |        P=0.124N         P=0.500          P=0.299N         P=0.674N         P=0.299N         P=0.299N        | 
|ORDER RESTRICTED   |        P=0.148N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 20      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Atrophy Focal                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/14 (0%)        0/15 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)        2/14 (14%)      | 
|POLY-3 RATE (b)    |        0/14.00          0/15.00          0/13.52          0/14.00          0/14.01          2/14.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             14.3%           | 
|TERMINAL (d)       |        0/14 (0%)        0/15 (0%)        0/13 (0%)        0/14 (0%)        0/14 (0%)        2/14 (14%)      | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.011 *        (e)              (e)              (e)              (e)              P=0.236         | 
|POLY 3             |        P=0.008 **       (e)              (e)              (e)              (e)              P=0.231         | 
|POLY 1.5           |        P=0.008 **       (e)              (e)              (e)              (e)              P=0.231         | 
|POLY 6             |        P=0.008 **       (e)              (e)              (e)              (e)              P=0.231         | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              P=0.236         | 
|COCH-ARM / FISHERS |        P=0.010 *        (e)              (e)              (e)              (e)              P=0.241         | 
|ORDER RESTRICTED   |        P=0.008 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Atrophy Focal                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/14 (7%)        0/14 (0%)        0/14 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        1/13.00          0/14.00          0/14.00          0/15.00          0/15.00          0/15.00         | 
|POLY-3 PERCENT (g) |        7.7%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        1/13 (8%)        0/14 (0%)        0/14 (0%)        0/15 (0%)        0/15 (0%)        0/15 (0%)       | 
|FIRST INCIDENCE    |        275 (T)          ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.402N         P=0.485N         P=0.485N         P=0.471N         P=0.471N         P=0.471N        | 
|POLY 3             |        P=0.424N         P=0.485N         P=0.485N         P=0.471N         P=0.471N         P=0.471N        | 
|POLY 1.5           |        P=0.423N         P=0.486N         P=0.486N         P=0.472N         P=0.472N         P=0.472N        | 
|POLY 6             |        P=0.424N         P=0.485N         P=0.485N         P=0.471N         P=0.471N         P=0.471N        | 
|LOGISTIC REGRESSION|        P=0.402N         (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.406N         P=0.500N         P=0.500N         P=0.483N         P=0.483N         P=0.483N        | 
|ORDER RESTRICTED   |        P=0.047N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 21      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland                                                                                                                    | 
|     Ectopic Thymus                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/14 (0%)        0/15 (0%)        0/15 (0%)        0/14 (0%)        0/14 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/14.00          0/15.00          0/13.52          0/14.00          0/14.00          0/14.02         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/14 (0%)        0/15 (0%)        0/13 (0%)        0/14 (0%)        0/14 (0%)        0/14 (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               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland                                                                                                                    | 
|     Ectopic Thymus                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/14 (14%)       1/13 (8%)        1/14 (7%)        3/14 (21%)       1/13 (8%)        2/15 (13%)      | 
|POLY-3 RATE (b)    |        2/13.00          1/13.00          1/13.23          3/14.00          1/13.00          2/15.00         | 
|POLY-3 PERCENT (g) |        15.4%            7.7%             7.6%             21.4%            7.7%             13.3%           | 
|TERMINAL (d)       |        2/13 (15%)       1/13 (8%)        1/13 (8%)        3/14 (21%)       1/13 (8%)        2/15 (13%)      | 
|FIRST INCIDENCE    |        275 (T)          275 (T)          275 (T)          275 (T)          275 (T)          275 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.575          P=0.500N         P=0.500N         P=0.536          P=0.500N         P=0.648N        | 
|POLY 3             |        P=0.572          P=0.500N         P=0.494N         P=0.535          P=0.500N         P=0.645N        | 
|POLY 1.5           |        P=0.568          P=0.501N         P=0.488N         P=0.534          P=0.501N         P=0.647N        | 
|POLY 6             |        P=0.575          P=0.500N         P=0.499N         P=0.535          P=0.500N         P=0.645N        | 
|LOGISTIC REGRESSION|        P=0.575          P=0.500N         P=0.500N         P=0.536          P=0.500N         P=0.648N        | 
|COCH-ARM / FISHERS |        P=0.551          P=0.529N         P=0.500N         P=0.500          P=0.529N         P=0.674N        | 
|ORDER RESTRICTED   |        P=0.636N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 02                                            Page 22      
Statistical Analysis of Non-neoplastic Lesions in       Mice(P53 Heterozygous Transgenic)  -        TRANSGENIC MODEL EVALUATION II (
ASPA                                                                                                                                
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              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               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus: Endometrium                                                                                                              | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        14/15 (93%)      14/15 (93%)      15/15 (100%)     14/15 (93%)      15/15 (100%)     15/15 (100%)    | 
|POLY-3 RATE (b)    |        14/14.00         14/14.05         15/15.00         14/15.00         15/15.00         15/15.00        | 
|POLY-3 PERCENT (g) |        100.0%           99.7%            100.0%           93.3%            100.0%           100.0%          | 
|TERMINAL (d)       |        14/14 (100%)     14/14 (100%)     14/14 (100%)     14/15 (93%)      15/15 (100%)     15/15 (100%)    | 
|FIRST INCIDENCE    |        275 (T)          275 (T)          168              275 (T)          275 (T)          275 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.603N         P=1.000N         P=0.514          P=0.514N         P=1.000N         P=1.000N        | 
|POLY 3             |        P=0.673          P=1.000N         P=1.000          P=0.515N         P=1.000          P=1.000         | 
|POLY 1.5           |        P=0.609          P=1.000N         P=1.000          P=0.532N         P=1.000          P=1.000         | 
|POLY 6             |        P=0.686          P=1.000N         P=1.000          P=0.514N         P=1.000          P=1.000         | 
|LOGISTIC REGRESSION|        P=0.715          P=1.000N         (e)              P=0.514N         P=1.000N         P=1.000N        | 
|COCH-ARM / FISHERS |        P=0.243          P=0.759N         P=0.500          P=0.759N         P=0.500          P=0.500         | 
|ORDER RESTRICTED   |        P=0.528N         (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).