https://ntp.niehs.nih.gov/go/6877

TDMS Study 99033-01 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: 01                                                                                     TIME: 11:29:50       
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 TG.AC MICE                                                         
               REASONS FOR REMOVAL:    ALL                                                                                          
               REMOVAL DATE RANGE:     ALL                                                                                          
               TREATMENT GROUPS:       INCLUDE 001    VEHICLE CONTROL                                                               
                                       INCLUDE 002    3125 PPM                                                                      
                                       INCLUDE 003    6250 PPM                                                                      
                                       INCLUDE 004    12500   PPM                                                                   
                                       INCLUDE 005    25000   PPM                                                                   
                                       INCLUDE 006    50000   PPM                                                                   
                                       INCLUDE 008    VEHICLE CONTROL                                                               
                                       INCLUDE 009    3125 PPM                                                                      
                                       INCLUDE 010    6250 PPM                                                                      
                                       INCLUDE 011    12500   PPM                                                                   
                                       INCLUDE 012    25000   PPM                                                                   
                                       INCLUDE 013    50000   PPM                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: BIORELIANCE                               TRANSGENIC MODEL EVALUATION II (ASPARTAME)                      DATE: 03/05/03       
EXPERIMENT: 99033 TEST: 01                                                                                     TIME: 11:29:50       
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                                                                                      
                                       Hypertrophy Focal                                                                            
Bone Marrow                            Hyperplasia                                                                                  
Kidney                                 Nephropathy                                                                                  
Liver                                  Necrosis Focal                                                                               
Lymph Node, Mandibular                 Necrosis                                                                                     
Spleen                                 Hematopoietic Cell Proliferation                                                             
Thymus                                 Atrophy Focal                                                                                
Thyroid Gland: Follicle                Cyst                                                                                         
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Adrenal Cortex                         Atrophy                                                                                      
Adrenal Cortex: Subcapsular            Hyperplasia Focal                                                                            
Liver                                  Necrosis Focal                                                                               
Liver: Hepatocyte                      Necrosis Focal                                                                               
Pituitary Gland                        Cyst                                                                                         
Spleen                                 Hematopoietic Cell Proliferation                                                             
===============================================================                                                                     
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions in        Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -        TRANSGENIC MODEL EVALUATION I
I (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)        |        10/13 (77%)      12/15 (80%)      8/13 (62%)       9/14 (64%)       8/15 (53%)       6/13 (46%)      | 
|POLY-3 RATE (b)    |        10/11.96         12/14.31         8/10.06          9/13.39          8/12.70          6/10.92         | 
|POLY-3 PERCENT (g) |        83.6%            83.8%            79.5%            67.2%            63.0%            54.9%           | 
|TERMINAL (d)       |        9/9 (100%)       12/12 (100%)     8/8 (100%)       9/12 (75%)       8/11 (73%)       6/9 (67%)       | 
|FIRST INCIDENCE    |        271              274 (T)          274 (T)          274 (T)          274 (T)          274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.006N**       P=0.469N         P=0.557N         P=0.086N         P=0.082N         P=0.061N        | 
|POLY 3             |        P=0.036N*        P=0.697          P=0.625N         P=0.311N         P=0.237N         P=0.138N        | 
|POLY 1.5           |        P=0.030N*        P=0.689N         P=0.470N         P=0.307N         P=0.202N         P=0.105N        | 
|POLY 6             |        P=0.046N*        P=0.675          P=0.694          P=0.329N         P=0.275N         P=0.187N        | 
|LOGISTIC REGRESSION|        (e)              P=0.469N         P=0.557N         P=0.086N         P=0.082N         P=0.061N        | 
|COCH-ARM / FISHERS |        P=0.033N*        P=0.600          P=0.336N         P=0.385N         P=0.184N         P=0.113N        | 
|ORDER RESTRICTED   |        P=0.097N         (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)        |        3/15 (20%)       2/12 (17%)       1/13 (8%)        4/13 (31%)       5/14 (36%)       5/15 (33%)      | 
|POLY-3 RATE (b)    |        3/13.74          2/12.00          1/9.84           4/11.37          5/13.92          5/10.74         | 
|POLY-3 PERCENT (g) |        21.8%            16.7%            10.2%            35.2%            35.9%            46.6%           | 
|TERMINAL (d)       |        1/11 (9%)        0/10 (0%)        1/9 (11%)        3/9 (33%)        3/11 (27%)       3/8 (38%)       | 
|FIRST INCIDENCE    |        200              198              275 (T)          165              269              184             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.039 *        P=0.544N         P=0.392N         P=0.385          P=0.362          P=0.199         | 
|POLY 3             |        P=0.043 *        P=0.565N         P=0.428N         P=0.387          P=0.348          P=0.198         | 
|POLY 1.5           |        P=0.053          P=0.576N         P=0.412N         P=0.398          P=0.336          P=0.228         | 
|POLY 6             |        P=0.040 *        P=0.555N         P=0.442N         P=0.380          P=0.357          P=0.185         | 
|LOGISTIC REGRESSION|        P=0.074          P=0.698N         P=0.373N         P=0.423          P=0.281          P=0.253         | 
|COCH-ARM / FISHERS |        P=0.100          P=0.612N         P=0.356N         P=0.412          P=0.298          P=0.341         | 
|ORDER RESTRICTED   |        P=0.083          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 2       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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)        |        9/13 (69%)       5/15 (33%)       5/13 (38%)       6/14 (43%)       7/15 (47%)       5/13 (38%)      | 
|POLY-3 RATE (b)    |        9/11.92          5/14.31          5/10.06          6/13.39          7/12.70          5/10.92         | 
|POLY-3 PERCENT (g) |        75.5%            34.9%            49.7%            44.8%            55.1%            45.8%           | 
|TERMINAL (d)       |        9/9 (100%)       5/12 (42%)       5/8 (63%)        6/12 (50%)       7/11 (64%)       5/9 (56%)       | 
|FIRST INCIDENCE    |        274 (T)          274 (T)          274 (T)          274 (T)          274 (T)          274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.350N         P=0.011N*        P=0.089N         P=0.024N*        P=0.077N         P=0.049N*       | 
|POLY 3             |        P=0.415N         P=0.038N*        P=0.204N         P=0.118N         P=0.261N         P=0.145N        | 
|POLY 1.5           |        P=0.378N         P=0.038N*        P=0.149N         P=0.118N         P=0.231N         P=0.116N        | 
|POLY 6             |        P=0.454N         P=0.039N*        P=0.268N         P=0.122N         P=0.290N         P=0.184N        | 
|LOGISTIC REGRESSION|        P=0.350N         P=0.011N*        P=0.089N         P=0.024N*        P=0.077N         P=0.049N*       | 
|COCH-ARM / FISHERS |        P=0.334N         P=0.064N         P=0.119N         P=0.161N         P=0.207N         P=0.119N        | 
|ORDER RESTRICTED   |        P=0.135N         (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%)        0/12 (0%)        0/13 (0%)        0/13 (0%)        0/14 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/13.08          0/11.33          0/9.84           0/10.59          0/13.80          0/9.98          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/11 (0%)        0/10 (0%)        0/9 (0%)         0/9 (0%)         0/11 (0%)        0/8 (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: 01                                            Page 3       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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)        |        0/13 (0%)        0/15 (0%)        0/13 (0%)        0/14 (0%)        0/15 (0%)        1/13 (8%)       | 
|POLY-3 RATE (b)    |        0/11.92          0/14.31          0/10.06          0/13.39          0/12.70          1/10.92         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             9.2%            | 
|TERMINAL (d)       |        0/9 (0%)         0/12 (0%)        0/8 (0%)         0/12 (0%)        0/11 (0%)        1/9 (11%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.093          (e)              (e)              (e)              (e)              P=0.500         | 
|POLY 3             |        P=0.095          (e)              (e)              (e)              (e)              P=0.482         | 
|POLY 1.5           |        P=0.097          (e)              (e)              (e)              (e)              P=0.493         | 
|POLY 6             |        P=0.092          (e)              (e)              (e)              (e)              P=0.472         | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              P=0.500         | 
|COCH-ARM / FISHERS |        P=0.099          (e)              (e)              (e)              (e)              P=0.500         | 
|ORDER RESTRICTED   |        P=0.052          (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%)      6/12 (50%)       6/13 (46%)       5/13 (38%)       6/14 (43%)       6/15 (40%)      | 
|POLY-3 RATE (b)    |        12/14.06         6/11.37          6/11.03          5/10.59          6/13.80          6/10.68         | 
|POLY-3 PERCENT (g) |        85.3%            52.8%            54.4%            47.2%            43.5%            56.2%           | 
|TERMINAL (d)       |        9/11 (82%)       5/10 (50%)       4/9 (44%)        5/9 (56%)        6/11 (55%)       5/8 (63%)       | 
|FIRST INCIDENCE    |        200              271              200              275 (T)          275 (T)          184             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.304N         P=0.085N         P=0.166N         P=0.060N         P=0.037N*        P=0.222N        | 
|POLY 3             |        P=0.149N         P=0.078N         P=0.100N         P=0.046N*        P=0.019N*        P=0.117N        | 
|POLY 1.5           |        P=0.130N         P=0.077N         P=0.098N         P=0.030N*        P=0.022N*        P=0.073N        | 
|POLY 6             |        P=0.166N         P=0.088N         P=0.099N         P=0.066N         P=0.020N*        P=0.159N        | 
|LOGISTIC REGRESSION|        P=0.176N         P=0.065N         P=0.114N         P=0.036N*        P=0.023N*        P=0.101N        | 
|COCH-ARM / FISHERS |        P=0.086N         P=0.109N         P=0.071N         P=0.031N*        P=0.046N*        P=0.030N*       | 
|ORDER RESTRICTED   |        P=0.044N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 4       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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: Zona Reticularis                                                                                                 | 
|     Vacuolization Cytoplasmic                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/13 (0%)        0/15 (0%)        0/13 (0%)        0/14 (0%)        0/15 (0%)        0/13 (0%)       | 
|POLY-3 RATE (b)    |        0/11.92          0/14.31          0/10.06          0/13.39          0/12.70          0/10.92         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/9 (0%)         0/12 (0%)        0/8 (0%)         0/12 (0%)        0/11 (0%)        0/9 (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             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex: Zona Reticularis                                                                                                 | 
|     Vacuolization Cytoplasmic                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        12/15 (80%)      9/12 (75%)       6/13 (46%)       8/13 (62%)       9/14 (64%)       8/15 (53%)      | 
|POLY-3 RATE (b)    |        12/13.45         9/11.33          6/9.84           8/10.59          9/13.85          8/12.10         | 
|POLY-3 PERCENT (g) |        89.2%            79.4%            61.0%            75.6%            65.0%            66.1%           | 
|TERMINAL (d)       |        10/11 (91%)      9/10 (90%)       6/9 (67%)        8/9 (89%)        8/11 (73%)       4/8 (50%)       | 
|FIRST INCIDENCE    |        242              275 (T)          275 (T)          275 (T)          270              151             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.548          P=0.312N         P=0.090N         P=0.309N         P=0.209N         P=0.508N        | 
|POLY 3             |        P=0.152N         P=0.452N         P=0.119N         P=0.358N         P=0.139N         P=0.168N        | 
|POLY 1.5           |        P=0.179N         P=0.474N         P=0.103N         P=0.299N         P=0.177N         P=0.170N        | 
|POLY 6             |        P=0.117N         P=0.456N         P=0.141N         P=0.417N         P=0.118N         P=0.147N        | 
|LOGISTIC REGRESSION|        P=0.423N         P=0.361N         P=0.115N         P=0.338N         P=0.088N         P=0.313N        | 
|COCH-ARM / FISHERS |        P=0.173N         P=0.557N         P=0.071N         P=0.255N         P=0.298N         P=0.123N        | 
|ORDER RESTRICTED   |        P=0.125N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 5       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone Marrow                                                                                                                      | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/14 (0%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         2/14 (14%)      | 
|POLY-3 RATE (b)    |        0/12.30          0/0.00           0/0.00           0/0.00           0/0.00           2/13.36         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             15.0%           | 
|TERMINAL (d)       |        0/9 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/10 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              180             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.012 *        (e)              (e)              (e)              (e)              P=0.252         | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              P=0.250         | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              P=0.246         | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              P=0.252         | 
|LOGISTIC REGRESSION|        P=0.058          (e)              (e)              (e)              (e)              P=0.126         | 
|COCH-ARM / FISHERS |        P=0.136          (e)              (e)              (e)              (e)              P=0.241         | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Bone Marrow                                                                                                                      | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/12 (0%)       | 
|POLY-3 RATE (b)    |        0/13.08          0/0.00           0/0.00           0/0.00           0/0.00           0/9.88          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/11 (0%)        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/8 (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: 01                                            Page 6       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Epididymis: Unilateral                                                                                                           | 
|     Aspermia                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        3/15 (20%)       4/15 (27%)       2/15 (13%)       3/15 (20%)       2/15 (13%)      | 
|POLY-3 RATE (b)    |        1/12.63          3/14.31          4/11.74          2/13.81          3/13.57          2/12.09         | 
|POLY-3 PERCENT (g) |        7.9%             21.0%            34.1%            14.5%            22.1%            16.5%           | 
|TERMINAL (d)       |        0/9 (0%)         3/12 (25%)       2/8 (25%)        1/12 (8%)        2/11 (18%)       1/10 (10%)      | 
|FIRST INCIDENCE    |        271              274 (T)          78               271              138              271             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.531N         P=0.398          P=0.146          P=0.552          P=0.334          P=0.492         | 
|POLY 3             |        P=0.570N         P=0.345          P=0.133          P=0.532          P=0.323          P=0.484         | 
|POLY 1.5           |        P=0.552N         P=0.333          P=0.143          P=0.526          P=0.315          P=0.494         | 
|POLY 6             |        P=0.565          P=0.353          P=0.129          P=0.534          P=0.329          P=0.476         | 
|LOGISTIC REGRESSION|        P=0.528N         P=0.357          P=0.188          P=0.536          P=0.294          P=0.476         | 
|COCH-ARM / FISHERS |        P=0.531N         P=0.299          P=0.165          P=0.500          P=0.299          P=0.500         | 
|ORDER RESTRICTED   |        P=0.373          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Epididymis: Unilateral                                                                                                           | 
|     Aspermia                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                                                                                                             | 
|POLY-3 RATE (b)    |                                                                                                             | 
|POLY-3 PERCENT (g) |                                                                                                             | 
|TERMINAL (d)       |                                                                                                             | 
|FIRST INCIDENCE    |                                                                                                             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                                                                                                             | 
|POLY 3             |                                                                                                             | 
|POLY 1.5           |                                                                                                             | 
|POLY 6             |                                                                                                             | 
|LOGISTIC REGRESSION|                                                                                                             | 
|COCH-ARM / FISHERS |                                                                                                             | 
|ORDER RESTRICTED   |                                                                                                             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 7       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Epididymis: Unilateral                                                                                                           | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        2/15 (13%)       0/15 (0%)        0/15 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/12.59          0/14.31          2/10.77          0/13.78          0/12.70          0/12.06         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             18.6%            0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/9 (0%)         0/12 (0%)        1/8 (13%)        0/12 (0%)        0/11 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        ---              ---              207              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.384N         (e)              P=0.207          (e)              (e)              (e)             | 
|POLY 3             |        P=0.431N         (e)              P=0.194          (e)              (e)              (e)             | 
|POLY 1.5           |        P=0.418N         (e)              P=0.204          (e)              (e)              (e)             | 
|POLY 6             |        P=0.437N         (e)              P=0.190          (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        P=0.379N         (e)              P=0.222          (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.381N         (e)              P=0.241          (e)              (e)              (e)             | 
|ORDER RESTRICTED   |        P=0.364N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Epididymis: Unilateral                                                                                                           | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                                                                                                             | 
|POLY-3 RATE (b)    |                                                                                                             | 
|POLY-3 PERCENT (g) |                                                                                                             | 
|TERMINAL (d)       |                                                                                                             | 
|FIRST INCIDENCE    |                                                                                                             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                                                                                                             | 
|POLY 3             |                                                                                                             | 
|POLY 1.5           |                                                                                                             | 
|POLY 6             |                                                                                                             | 
|LOGISTIC REGRESSION|                                                                                                             | 
|COCH-ARM / FISHERS |                                                                                                             | 
|ORDER RESTRICTED   |                                                                                                             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 8       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Eye: Retina                                                                                                                      | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        12/12 (100%)     0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         14/14 (100%)    | 
|POLY-3 RATE (b)    |        12/12.00         0/0.00           0/0.00           0/0.00           0/0.00           14/14.00        | 
|POLY-3 PERCENT (g) |        100.0%           0.0%             0.0%             0.0%             0.0%             100.0%          | 
|TERMINAL (d)       |        9/9 (100%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         10/10 (100%)    | 
|FIRST INCIDENCE    |        271              ---              ---              ---              ---              180             | 
|-------------------|                                                                                                             | 
|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             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Eye: Retina                                                                                                                      | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        15/15 (100%)     0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         10/10 (100%)    | 
|POLY-3 RATE (b)    |        15/15.00         0/0.00           0/0.00           0/0.00           0/0.00           10/10.00        | 
|POLY-3 PERCENT (g) |        100.0%           0.0%             0.0%             0.0%             0.0%             100.0%          | 
|TERMINAL (d)       |        11/11 (100%)     0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         8/8 (100%)      | 
|FIRST INCIDENCE    |        109              ---              ---              ---              ---              184             | 
|-------------------|                                                                                                             | 
|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: 01                                            Page 9       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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)        |        3/15 (20%)       0/15 (0%)        0/13 (0%)        0/15 (0%)        0/14 (0%)        1/15 (7%)       | 
|POLY-3 RATE (b)    |        3/12.66          0/14.31          0/10.06          0/13.78          0/12.66          1/12.06         | 
|POLY-3 PERCENT (g) |        23.7%            0.0%             0.0%             0.0%             0.0%             8.3%            | 
|TERMINAL (d)       |        1/9 (11%)        0/12 (0%)        0/8 (0%)         0/12 (0%)        0/11 (0%)        1/10 (10%)      | 
|FIRST INCIDENCE    |        271              ---              ---              ---              ---              274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.485N         P=0.088N         P=0.164N         P=0.096N         P=0.118N         P=0.300N        | 
|POLY 3             |        P=0.473N         P=0.083N         P=0.147N         P=0.089N         P=0.103N         P=0.313N        | 
|POLY 1.5           |        P=0.476N         P=0.088N         P=0.139N         P=0.092N         P=0.106N         P=0.302N        | 
|POLY 6             |        P=0.469N         P=0.080N         P=0.156N         P=0.088N         P=0.101N         P=0.323N        | 
|LOGISTIC REGRESSION|        P=0.494N         P=0.086N         P=0.156N         P=0.094N         P=0.107N         P=0.317N        | 
|COCH-ARM / FISHERS |        P=0.470N         P=0.112N         P=0.139N         P=0.112N         P=0.125N         P=0.299N        | 
|ORDER RESTRICTED   |        P=0.008N**       (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)        |        1/15 (7%)        0/12 (0%)        0/13 (0%)        0/14 (0%)        0/14 (0%)        1/14 (7%)       | 
|POLY-3 RATE (b)    |        1/13.08          0/11.33          0/9.84           0/10.80          0/13.80          1/9.94          | 
|POLY-3 PERCENT (g) |        7.7%             0.0%             0.0%             0.0%             0.0%             10.1%           | 
|TERMINAL (d)       |        1/11 (9%)        0/10 (0%)        0/9 (0%)         0/9 (0%)         0/11 (0%)        1/8 (13%)       | 
|FIRST INCIDENCE    |        275 (T)          ---              ---              ---              ---              275 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.375          P=0.519N         P=0.540N         P=0.540N         P=0.500N         P=0.693         | 
|POLY 3             |        P=0.410          P=0.529N         P=0.556N         P=0.538N         P=0.489N         P=0.698         | 
|POLY 1.5           |        P=0.413          P=0.533N         P=0.552N         P=0.529N         P=0.497N         P=0.711         | 
|POLY 6             |        P=0.408          P=0.525N         P=0.558N         P=0.542N         P=0.483N         P=0.691         | 
|LOGISTIC REGRESSION|        P=0.375          (e)              (e)              (e)              (e)              P=0.693         | 
|COCH-ARM / FISHERS |        P=0.422          P=0.556N         P=0.536N         P=0.517N         P=0.517N         P=0.741         | 
|ORDER RESTRICTED   |        P=0.217          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 10      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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)        |        1/15 (7%)        0/15 (0%)        1/13 (8%)        0/15 (0%)        0/14 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        1/12.59          0/14.31          1/10.06          0/13.78          0/12.66          0/12.06         | 
|POLY-3 PERCENT (g) |        7.9%             0.0%             9.9%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        1/9 (11%)        0/12 (0%)        1/8 (13%)        0/12 (0%)        0/11 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        274 (T)          ---              274 (T)          ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.278N         P=0.443N         P=0.741          P=0.443N         P=0.460N         P=0.479N        | 
|POLY 3             |        P=0.300N         P=0.474N         P=0.711          P=0.482N         P=0.499N         P=0.509N        | 
|POLY 1.5           |        P=0.297N         P=0.481N         P=0.720          P=0.485N         P=0.502N         P=0.503N        | 
|POLY 6             |        P=0.302N         P=0.470N         P=0.703          P=0.481N         P=0.497N         P=0.513N        | 
|LOGISTIC REGRESSION|        P=0.278N         (e)              P=0.741          (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.285N         P=0.500N         P=0.722          P=0.500N         P=0.517N         P=0.500N        | 
|ORDER RESTRICTED   |        P=0.198N         (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)        |        1/15 (7%)        2/12 (17%)       1/13 (8%)        0/14 (0%)        0/14 (0%)        1/14 (7%)       | 
|POLY-3 RATE (b)    |        1/13.08          2/11.33          1/9.84           0/10.80          0/13.80          1/9.94          | 
|POLY-3 PERCENT (g) |        7.7%             17.7%            10.2%            0.0%             0.0%             10.1%           | 
|TERMINAL (d)       |        1/11 (9%)        2/10 (20%)       1/9 (11%)        0/9 (0%)         0/11 (0%)        1/8 (13%)       | 
|FIRST INCIDENCE    |        275 (T)          275 (T)          275 (T)          ---              ---              275 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.495N         P=0.465          P=0.720          P=0.540N         P=0.500N         P=0.693         | 
|POLY 3             |        P=0.369N         P=0.448          P=0.696          P=0.538N         P=0.489N         P=0.698         | 
|POLY 1.5           |        P=0.389N         P=0.441          P=0.701          P=0.529N         P=0.497N         P=0.711         | 
|POLY 6             |        P=0.354N         P=0.455          P=0.694          P=0.542N         P=0.483N         P=0.691         | 
|LOGISTIC REGRESSION|        P=0.495N         P=0.465          P=0.720          (e)              (e)              P=0.693         | 
|COCH-ARM / FISHERS |        P=0.427N         P=0.414          P=0.722          P=0.517N         P=0.517N         P=0.741         | 
|ORDER RESTRICTED   |        P=0.364N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 11      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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 Acute Focal                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        0/15 (0%)        0/14 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        1/12.59          0/14.31          0/10.17          0/13.78          0/12.66          0/12.06         | 
|POLY-3 PERCENT (g) |        7.9%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        1/9 (11%)        0/12 (0%)        0/8 (0%)         0/12 (0%)        0/11 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        274 (T)          ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.410N         P=0.443N         P=0.523N         P=0.443N         P=0.460N         P=0.479N        | 
|POLY 3             |        P=0.403N         P=0.474N         P=0.542N         P=0.482N         P=0.499N         P=0.509N        | 
|POLY 1.5           |        P=0.411N         P=0.481N         P=0.531N         P=0.485N         P=0.502N         P=0.503N        | 
|POLY 6             |        P=0.398N         P=0.470N         P=0.551N         P=0.481N         P=0.497N         P=0.513N        | 
|LOGISTIC REGRESSION|        P=0.410N         (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.416N         P=0.500N         P=0.517N         P=0.500N         P=0.517N         P=0.500N        | 
|ORDER RESTRICTED   |        P=0.069N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation Acute Focal                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        0/15 (0%)        0/14 (0%)        0/15 (0%)        1/14 (7%)        2/14 (14%)      | 
|POLY-3 RATE (b)    |        1/13.08          0/12.12          0/9.99           0/10.85          1/13.88          2/11.62         | 
|POLY-3 PERCENT (g) |        7.7%             0.0%             0.0%             0.0%             7.2%             17.2%           | 
|TERMINAL (d)       |        1/11 (9%)        0/10 (0%)        0/9 (0%)         0/9 (0%)         0/11 (0%)        0/8 (0%)        | 
|FIRST INCIDENCE    |        275 (T)          ---              ---              ---              267              79              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.066          P=0.519N         P=0.540N         P=0.540N         P=0.743N         P=0.436         | 
|POLY 3             |        P=0.080          P=0.515N         P=0.553N         P=0.537N         P=0.747N         P=0.458         | 
|POLY 1.5           |        P=0.076          P=0.510N         P=0.545N         P=0.526N         P=0.756N         P=0.461         | 
|POLY 6             |        P=0.084          P=0.519N         P=0.557N         P=0.542N         P=0.739N         P=0.458         | 
|LOGISTIC REGRESSION|        P=0.084          (e)              (e)              (e)              P=0.763N         P=0.677         | 
|COCH-ARM / FISHERS |        P=0.068          P=0.500N         P=0.517N         P=0.500N         P=0.741          P=0.473         | 
|ORDER RESTRICTED   |        P=0.079          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 12      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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 Focal                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/12.59          0/14.31          0/10.17          0/13.78          0/12.66          0/12.06         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/9 (0%)         0/12 (0%)        0/8 (0%)         0/12 (0%)        0/11 (0%)        0/10 (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                                                                                                                            | 
|     Inflammation Chronic Focal                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/15 (13%)       0/15 (0%)        0/14 (0%)        0/15 (0%)        1/14 (7%)        1/14 (7%)       | 
|POLY-3 RATE (b)    |        2/13.74          0/12.12          0/9.99           0/10.85          1/13.86          1/9.94          | 
|POLY-3 PERCENT (g) |        14.6%            0.0%             0.0%             0.0%             7.2%             10.1%           | 
|TERMINAL (d)       |        0/11 (0%)        0/10 (0%)        0/9 (0%)         0/9 (0%)         0/11 (0%)        1/8 (13%)       | 
|FIRST INCIDENCE    |        200              ---              ---              ---              269              275 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.476          P=0.267N         P=0.300N         P=0.298N         P=0.491N         P=0.621N        | 
|POLY 3             |        P=0.500          P=0.260N         P=0.309N         P=0.288N         P=0.497N         P=0.613N        | 
|POLY 1.5           |        P=0.501          P=0.250N         P=0.293N         P=0.269N         P=0.504N         P=0.588N        | 
|POLY 6             |        P=0.503          P=0.272N         P=0.321N         P=0.301N         P=0.493N         P=0.630N        | 
|LOGISTIC REGRESSION|        P=0.500          P=0.215N         P=0.228N         P=0.209N         P=0.636N         P=0.543N        | 
|COCH-ARM / FISHERS |        P=0.507          P=0.241N         P=0.259N         P=0.241N         P=0.527N         P=0.527N        | 
|ORDER RESTRICTED   |        P=0.233N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 13      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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)        |        0/15 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)        0/14 (0%)        2/15 (13%)      | 
|POLY-3 RATE (b)    |        0/12.59          0/14.31          0/10.17          0/13.78          0/12.66          2/12.06         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             16.6%           | 
|TERMINAL (d)       |        0/9 (0%)         0/12 (0%)        0/8 (0%)         0/12 (0%)        0/11 (0%)        2/10 (20%)      | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.010 *        (e)              (e)              (e)              (e)              P=0.257         | 
|POLY 3             |        P=0.009 **       (e)              (e)              (e)              (e)              P=0.219         | 
|POLY 1.5           |        P=0.009 **       (e)              (e)              (e)              (e)              P=0.226         | 
|POLY 6             |        P=0.009 **       (e)              (e)              (e)              (e)              P=0.214         | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              P=0.257         | 
|COCH-ARM / FISHERS |        P=0.011 *        (e)              (e)              (e)              (e)              P=0.241         | 
|ORDER RESTRICTED   |        P=0.006 **       (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)        |        1/15 (7%)        0/15 (0%)        0/14 (0%)        0/15 (0%)        0/14 (0%)        4/14 (29%)      | 
|POLY-3 RATE (b)    |        1/13.08          0/12.12          0/9.99           0/10.85          0/13.80          4/10.90         | 
|POLY-3 PERCENT (g) |        7.7%             0.0%             0.0%             0.0%             0.0%             36.7%           | 
|TERMINAL (d)       |        1/11 (9%)        0/10 (0%)        0/9 (0%)         0/9 (0%)         0/11 (0%)        3/8 (38%)       | 
|FIRST INCIDENCE    |        275 (T)          ---              ---              ---              ---              92              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.519N         P=0.540N         P=0.540N         P=0.500N         P=0.095         | 
|POLY 3             |        P<0.001 **       P=0.515N         P=0.553N         P=0.537N         P=0.489N         P=0.103         | 
|POLY 1.5           |        P<0.001 **       P=0.510N         P=0.545N         P=0.526N         P=0.497N         P=0.113         | 
|POLY 6             |        P<0.001 **       P=0.519N         P=0.557N         P=0.542N         P=0.483N         P=0.097         | 
|LOGISTIC REGRESSION|        P=0.002 **       (e)              (e)              (e)              (e)              P=0.144         | 
|COCH-ARM / FISHERS |        P=0.002 **       P=0.500N         P=0.517N         P=0.500N         P=0.517N         P=0.143         | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 14      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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%)        0/14 (0%)        0/15 (0%)        0/14 (0%)        0/15 (0%)       | 
|POLY-3 RATE (b)    |        0/12.59          0/14.31          0/10.17          0/13.78          0/12.66          0/12.06         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/9 (0%)         0/12 (0%)        0/8 (0%)         0/12 (0%)        0/11 (0%)        0/10 (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%)        1/15 (7%)        0/14 (0%)        4/15 (27%)       1/14 (7%)        0/14 (0%)       | 
|POLY-3 RATE (b)    |        0/13.08          1/12.12          0/9.99           4/11.68          1/13.80          0/9.94          | 
|POLY-3 PERCENT (g) |        0.0%             8.3%             0.0%             34.3%            7.3%             0.0%            | 
|TERMINAL (d)       |        0/11 (0%)        1/10 (10%)       0/9 (0%)         2/9 (22%)        1/11 (9%)        0/8 (0%)        | 
|FIRST INCIDENCE    |        ---              275 (T)          ---              165              275 (T)          ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.502N         P=0.481          (e)              P=0.048 *        P=0.500          (e)             | 
|POLY 3             |        P=0.488N         P=0.485          (e)              P=0.030 *        P=0.511          (e)             | 
|POLY 1.5           |        P=0.483N         P=0.490          (e)              P=0.033 *        P=0.503          (e)             | 
|POLY 6             |        P=0.486N         P=0.480          (e)              P=0.029 *        P=0.517          (e)             | 
|LOGISTIC REGRESSION|        P=0.470N         P=0.481          (e)              P=0.048 *        P=0.500          (e)             | 
|COCH-ARM / FISHERS |        P=0.460N         P=0.500          (e)              P=0.050          P=0.483          (e)             | 
|ORDER RESTRICTED   |        P=0.191          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 15      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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                                                                                                                             | 
|     Hemorrhage Focal                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/14 (0%)        3/15 (20%)       0/14 (0%)        0/15 (0%)        1/14 (7%)        0/14 (0%)       | 
|POLY-3 RATE (b)    |        0/12.30          3/14.94          0/10.17          0/13.78          1/12.79          0/11.92         | 
|POLY-3 PERCENT (g) |        0.0%             20.1%            0.0%             0.0%             7.8%             0.0%            | 
|TERMINAL (d)       |        0/9 (0%)         2/12 (17%)       0/8 (0%)         0/12 (0%)        0/11 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        ---              198              ---              ---              261              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.303N         P=0.171          (e)              (e)              P=0.500          (e)             | 
|POLY 3             |        P=0.258N         P=0.144          (e)              (e)              P=0.508          (e)             | 
|POLY 1.5           |        P=0.267N         P=0.138          (e)              (e)              P=0.507          (e)             | 
|POLY 6             |        P=0.253N         P=0.150          (e)              (e)              P=0.508          (e)             | 
|LOGISTIC REGRESSION|        P=0.307N         P=0.093          (e)              (e)              P=0.502          (e)             | 
|COCH-ARM / FISHERS |        P=0.305N         P=0.125          (e)              (e)              P=0.500          (e)             | 
|ORDER RESTRICTED   |        P=0.192N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Hemorrhage Focal                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        0/14 (0%)        0/14 (0%)        0/15 (0%)        0/14 (0%)        0/14 (0%)       | 
|POLY-3 RATE (b)    |        1/13.08          0/12.09          0/9.99           0/10.85          0/13.80          0/9.94          | 
|POLY-3 PERCENT (g) |        7.7%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        1/11 (9%)        0/10 (0%)        0/9 (0%)         0/9 (0%)         0/11 (0%)        0/8 (0%)        | 
|FIRST INCIDENCE    |        275 (T)          ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.437N         P=0.519N         P=0.540N         P=0.540N         P=0.500N         P=0.564N        | 
|POLY 3             |        P=0.332N         P=0.516N         P=0.553N         P=0.537N         P=0.489N         P=0.554N        | 
|POLY 1.5           |        P=0.359N         P=0.513N         P=0.545N         P=0.526N         P=0.497N         P=0.544N        | 
|POLY 6             |        P=0.314N         P=0.520N         P=0.557N         P=0.542N         P=0.483N         P=0.560N        | 
|LOGISTIC REGRESSION|        P=0.437N         (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.420N         P=0.517N         P=0.517N         P=0.500N         P=0.517N         P=0.517N        | 
|ORDER RESTRICTED   |        P=0.112N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 16      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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)        |        1/12 (8%)        2/15 (13%)       0/13 (0%)        2/14 (14%)       0/14 (0%)        1/14 (7%)       | 
|POLY-3 RATE (b)    |        1/10.96          2/14.97          0/9.17           2/13.97          0/12.66          1/12.64         | 
|POLY-3 PERCENT (g) |        9.1%             13.4%            0.0%             14.3%            0.0%             7.9%            | 
|TERMINAL (d)       |        0/8 (0%)         0/12 (0%)        0/7 (0%)         1/12 (8%)        0/11 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        271              198              ---              199              ---              180             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.477N         P=0.562          P=0.557N         P=0.581          P=0.517N         P=0.759         | 
|POLY 3             |        P=0.419N         P=0.609          P=0.535N         P=0.585          P=0.471N         P=0.730N        | 
|POLY 1.5           |        P=0.424N         P=0.604          P=0.514N         P=0.581          P=0.467N         P=0.724N        | 
|POLY 6             |        P=0.421N         P=0.611          P=0.552N         P=0.587          P=0.477N         P=0.737N        | 
|LOGISTIC REGRESSION|        P=0.470N         P=0.531          P=0.551N         P=0.512          P=0.471N         P=0.759N        | 
|COCH-ARM / FISHERS |        P=0.448N         P=0.586          P=0.480N         P=0.560          P=0.462N         P=0.720N        | 
|ORDER RESTRICTED   |        P=0.472N         (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)        |        2/15 (13%)       2/14 (14%)       0/12 (0%)        2/12 (17%)       2/14 (14%)       1/12 (8%)       | 
|POLY-3 RATE (b)    |        2/13.74          2/12.72          0/9.18           2/11.07          2/13.95          1/10.14         | 
|POLY-3 PERCENT (g) |        14.6%            15.7%            0.0%             18.1%            14.3%            9.9%            | 
|TERMINAL (d)       |        0/11 (0%)        1/10 (10%)       0/9 (0%)         1/9 (11%)        0/11 (0%)        0/8 (0%)        | 
|FIRST INCIDENCE    |        200              198              ---              184              267              184             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.554N         P=0.655          P=0.311N         P=0.604          P=0.671N         P=0.612N        | 
|POLY 3             |        P=0.522N         P=0.671          P=0.329N         P=0.619          P=0.694N         P=0.607N        | 
|POLY 1.5           |        P=0.525N         P=0.676          P=0.323N         P=0.618          P=0.696          P=0.601N        | 
|POLY 6             |        P=0.518N         P=0.664          P=0.328N         P=0.622          P=0.688N         P=0.608N        | 
|LOGISTIC REGRESSION|        P=0.533N         P=0.658          P=0.261N         P=0.627          P=0.605          P=0.518N        | 
|COCH-ARM / FISHERS |        P=0.541N         P=0.674          P=0.299N         P=0.611          P=0.674          P=0.586N        | 
|ORDER RESTRICTED   |        P=0.639N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 17      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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                                                                                                           | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/12 (17%)       0/15 (0%)        0/13 (0%)        0/14 (0%)        0/14 (0%)        0/14 (0%)       | 
|POLY-3 RATE (b)    |        2/10.99          0/14.31          0/9.17           0/13.35          0/12.66          0/11.92         | 
|POLY-3 PERCENT (g) |        18.2%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/8 (0%)         0/12 (0%)        0/7 (0%)         0/12 (0%)        0/11 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        271              ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.217N         P=0.202N         P=0.300N         P=0.217N         P=0.254N         P=0.254N        | 
|POLY 3             |        P=0.171N         P=0.170N         P=0.272N         P=0.185N         P=0.196N         P=0.209N        | 
|POLY 1.5           |        P=0.180N         P=0.169N         P=0.245N         P=0.184N         P=0.192N         P=0.198N        | 
|POLY 6             |        P=0.162N         P=0.174N         P=0.297N         P=0.188N         P=0.203N         P=0.221N        | 
|LOGISTIC REGRESSION|        P=0.200N         P=0.174N         P=0.283N         P=0.188N         P=0.199N         P=0.215N        | 
|COCH-ARM / FISHERS |        P=0.197N         P=0.188N         P=0.220N         P=0.203N         P=0.203N         P=0.203N        | 
|ORDER RESTRICTED   |        P=0.005N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        0/14 (0%)        0/12 (0%)        0/12 (0%)        0/14 (0%)        0/12 (0%)       | 
|POLY-3 RATE (b)    |        0/13.08          0/12.09          0/9.18           0/10.37          0/13.80          0/9.44          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/11 (0%)        0/10 (0%)        0/9 (0%)         0/9 (0%)         0/11 (0%)        0/8 (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: 01                                            Page 18      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                                                                                                             | 
|POLY-3 RATE (b)    |                                                                                                             | 
|POLY-3 PERCENT (g) |                                                                                                             | 
|TERMINAL (d)       |                                                                                                             | 
|FIRST INCIDENCE    |                                                                                                             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                                                                                                             | 
|POLY 3             |                                                                                                             | 
|POLY 1.5           |                                                                                                             | 
|POLY 6             |                                                                                                             | 
|LOGISTIC REGRESSION|                                                                                                             | 
|COCH-ARM / FISHERS |                                                                                                             | 
|ORDER RESTRICTED   |                                                                                                             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/15 (13%)       0/15 (0%)        1/13 (8%)        0/14 (0%)        0/14 (0%)        0/14 (0%)       | 
|POLY-3 RATE (b)    |        2/13.45          0/12.12          1/10.45          0/10.63          0/13.80          0/9.94          | 
|POLY-3 PERCENT (g) |        14.9%            0.0%             9.6%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/11 (0%)        0/10 (0%)        0/9 (0%)         0/9 (0%)         0/11 (0%)        0/8 (0%)        | 
|FIRST INCIDENCE    |        242              ---              200              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.173N         P=0.268N         P=0.602N         P=0.290N         P=0.232N         P=0.328N        | 
|POLY 3             |        P=0.120N         P=0.255N         P=0.589N         P=0.287N         P=0.225N         P=0.304N        | 
|POLY 1.5           |        P=0.132N         P=0.246N         P=0.586N         P=0.274N         P=0.230N         P=0.287N        | 
|POLY 6             |        P=0.111N         P=0.265N         P=0.590N         P=0.295N         P=0.223N         P=0.318N        | 
|LOGISTIC REGRESSION|        P=0.158N         P=0.235N         P=0.535N         P=0.258N         P=0.266N         P=0.268N        | 
|COCH-ARM / FISHERS |        P=0.160N         P=0.241N         P=0.556N         P=0.259N         P=0.259N         P=0.259N        | 
|ORDER RESTRICTED   |        P=0.064N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 19      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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                                                                                                                  | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/9 (0%)         0/13 (0%)        0/6 (0%)         0/11 (0%)        0/13 (0%)        0/9 (0%)        | 
|POLY-3 RATE (b)    |        0/8.90           0/12.35          0/4.80           0/10.39          0/11.66          0/8.25          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/6 (0%)         0/11 (0%)        0/4 (0%)         0/9 (0%)         0/10 (0%)        0/7 (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                                                                                                                  | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/13 (15%)       0/11 (0%)        0/12 (0%)        0/10 (0%)        0/11 (0%)        0/9 (0%)        | 
|POLY-3 RATE (b)    |        2/11.69          0/9.37           0/9.83           0/8.47           0/10.85          0/8.24          | 
|POLY-3 PERCENT (g) |        17.1%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        2/10 (20%)       0/9 (0%)         0/9 (0%)         0/7 (0%)         0/9 (0%)         0/7 (0%)        | 
|FIRST INCIDENCE    |        275 (T)          ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.232N         P=0.257N         P=0.257N         P=0.316N         P=0.257N         P=0.316N        | 
|POLY 3             |        P=0.200N         P=0.281N         P=0.270N         P=0.306N         P=0.245N         P=0.312N        | 
|POLY 1.5           |        P=0.208N         P=0.279N         P=0.264N         P=0.299N         P=0.251N         P=0.311N        | 
|POLY 6             |        P=0.195N         P=0.281N         P=0.276N         P=0.312N         P=0.241N         P=0.313N        | 
|LOGISTIC REGRESSION|        P=0.232N         (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.233N         P=0.283N         P=0.260N         P=0.308N         P=0.283N         P=0.338N        | 
|ORDER RESTRICTED   |        P=0.026N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 20      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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)        |        3/14 (21%)       3/15 (20%)       8/13 (62%)       2/15 (13%)       8/14 (57%)       4/14 (29%)      | 
|POLY-3 RATE (b)    |        3/12.36          3/14.35          8/11.50          2/13.78          8/13.66          4/13.36         | 
|POLY-3 PERCENT (g) |        24.3%            20.9%            69.6%            14.5%            58.6%            30.0%           | 
|TERMINAL (d)       |        1/9 (11%)        2/12 (17%)       6/8 (75%)        2/12 (17%)       6/11 (55%)       2/10 (20%)      | 
|FIRST INCIDENCE    |        271              271              138              274 (T)          138              180             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.407          P=0.558N         P=0.046 *        P=0.406N         P=0.125          P=0.523         | 
|POLY 3             |        P=0.422          P=0.598N         P=0.026 *        P=0.448N         P=0.079          P=0.546         | 
|POLY 1.5           |        P=0.414          P=0.605N         P=0.030 *        P=0.446N         P=0.074          P=0.539         | 
|POLY 6             |        P=0.426          P=0.596N         P=0.022 *        P=0.455N         P=0.081          P=0.548         | 
|LOGISTIC REGRESSION|        P=0.384          P=0.597N         P=0.035 *        P=0.449N         P=0.062          P=0.494         | 
|COCH-ARM / FISHERS |        P=0.383          P=0.639N         P=0.041 *        P=0.465N         P=0.060          P=0.500         | 
|ORDER RESTRICTED   |        P=0.196          (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)        |        10/15 (67%)      4/14 (29%)       7/14 (50%)       6/12 (50%)       8/14 (57%)       5/14 (36%)      | 
|POLY-3 RATE (b)    |        10/14.06         4/12.09          7/10.98          6/12.00          8/14.00          5/10.00         | 
|POLY-3 PERCENT (g) |        71.1%            33.1%            63.8%            50.0%            57.1%            50.0%           | 
|TERMINAL (d)       |        7/11 (64%)       4/10 (40%)       6/9 (67%)        3/9 (33%)        5/11 (46%)       4/8 (50%)       | 
|FIRST INCIDENCE    |        200              275 (T)          67               165              267              269             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.440N         P=0.071N         P=0.470N         P=0.335N         P=0.367N         P=0.296N        | 
|POLY 3             |        P=0.417N         P=0.051N         P=0.516N         P=0.244N         P=0.356N         P=0.268N        | 
|POLY 1.5           |        P=0.390N         P=0.041N*        P=0.437N         P=0.258N         P=0.374N         P=0.195N        | 
|POLY 6             |        P=0.422N         P=0.072N         P=0.593N         P=0.240N         P=0.351N         P=0.335N        | 
|LOGISTIC REGRESSION|        P=0.320N         P=0.042N*        P=0.424N         P=0.292N         P=0.374N         P=0.201N        | 
|COCH-ARM / FISHERS |        P=0.272N         P=0.046N*        P=0.297N         P=0.315N         P=0.442N         P=0.097N        | 
|ORDER RESTRICTED   |        P=0.282N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 21      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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                                                                                                                           | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        9/14 (64%)       12/15 (80%)      8/13 (62%)       12/15 (80%)      13/14 (93%)      11/14 (79%)     | 
|POLY-3 RATE (b)    |        9/12.33          12/14.35         8/10.90          12/13.81         13/14.00         11/13.28        | 
|POLY-3 PERCENT (g) |        73.0%            83.7%            73.4%            86.9%            92.9%            82.8%           | 
|TERMINAL (d)       |        8/9 (89%)        11/12 (92%)      7/8 (88%)        11/12 (92%)      10/11 (91%)      8/10 (80%)      | 
|FIRST INCIDENCE    |        271              271              150              271              138              180             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.261          P=0.673          P=0.677          P=0.659          P=0.310          P=0.468         | 
|POLY 3             |        P=0.328          P=0.422          P=0.676          P=0.338          P=0.193          P=0.451         | 
|POLY 1.5           |        P=0.284          P=0.398          P=0.637N         P=0.351          P=0.151          P=0.430         | 
|POLY 6             |        P=0.383          P=0.434          P=0.633          P=0.310          P=0.234          P=0.471         | 
|LOGISTIC REGRESSION|        P=0.163          (e)              P=0.574          (e)              P=0.093          P=0.316         | 
|COCH-ARM / FISHERS |        P=0.202          P=0.298          P=0.598N         P=0.298          P=0.082          P=0.339         | 
|ORDER RESTRICTED   |        P=0.270          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        10/15 (67%)      10/14 (71%)      11/14 (79%)      10/12 (83%)      11/14 (79%)      9/14 (64%)      | 
|POLY-3 RATE (b)    |        10/13.39         10/12.09         11/12.58         10/11.22         11/13.80         9/10.00         | 
|POLY-3 PERCENT (g) |        74.7%            82.7%            87.4%            89.2%            79.7%            90.0%           | 
|TERMINAL (d)       |        9/11 (82%)       10/10 (100%)     8/9 (89%)        8/9 (89%)        11/11 (100%)     8/8 (100%)      | 
|FIRST INCIDENCE    |        242              275 (T)          61               165              275 (T)          269             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.399          P=0.503          P=0.214          P=0.339          P=0.509          P=0.302         | 
|POLY 3             |        P=0.355          P=0.495          P=0.367          P=0.341          P=0.557          P=0.333         | 
|POLY 1.5           |        P=0.442          P=0.543          P=0.382          P=0.327          P=0.507          P=0.463         | 
|POLY 6             |        P=0.309          P=0.414          P=0.352          P=0.358          P=0.583          P=0.239         | 
|LOGISTIC REGRESSION|        P=0.572N         P=0.466          P=0.271          P=0.214          P=0.675N         P=0.271         | 
|COCH-ARM / FISHERS |        P=0.410N         P=0.550          P=0.383          P=0.298          P=0.383          P=0.600N        | 
|ORDER RESTRICTED   |        P=0.277          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 22      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Bilateral, Germinal Epithelium                                                                                           | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        2/15 (13%)       0/15 (0%)        1/14 (7%)        0/15 (0%)        1/15 (7%)       | 
|POLY-3 RATE (b)    |        0/12.59          2/14.31          0/10.20          1/13.39          0/12.70          1/12.06         | 
|POLY-3 PERCENT (g) |        0.0%             14.0%            0.0%             7.5%             0.0%             8.3%            | 
|TERMINAL (d)       |        0/9 (0%)         2/12 (17%)       0/8 (0%)         1/12 (8%)        0/11 (0%)        1/10 (10%)      | 
|FIRST INCIDENCE    |        ---              274 (T)          ---              274 (T)          ---              274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.609          P=0.300          (e)              P=0.557          (e)              P=0.521         | 
|POLY 3             |        P=0.623          P=0.261          (e)              P=0.512          (e)              P=0.491         | 
|POLY 1.5           |        P=0.621          P=0.254          (e)              P=0.506          (e)              P=0.497         | 
|POLY 6             |        P=0.622          P=0.267          (e)              P=0.517          (e)              P=0.487         | 
|LOGISTIC REGRESSION|        (e)              P=0.300          (e)              P=0.557          (e)              P=0.521         | 
|COCH-ARM / FISHERS |        P=0.600          P=0.241          (e)              P=0.483          (e)              P=0.500         | 
|ORDER RESTRICTED   |        P=0.329          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Bilateral, Germinal Epithelium                                                                                           | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                                                                                                             | 
|POLY-3 RATE (b)    |                                                                                                             | 
|POLY-3 PERCENT (g) |                                                                                                             | 
|TERMINAL (d)       |                                                                                                             | 
|FIRST INCIDENCE    |                                                                                                             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                                                                                                             | 
|POLY 3             |                                                                                                             | 
|POLY 1.5           |                                                                                                             | 
|POLY 6             |                                                                                                             | 
|LOGISTIC REGRESSION|                                                                                                             | 
|COCH-ARM / FISHERS |                                                                                                             | 
|ORDER RESTRICTED   |                                                                                                             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 23      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Germinal Epithelium                                                                                                      | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/15 (0%)        2/15 (13%)       0/15 (0%)        1/14 (7%)        0/15 (0%)        1/15 (7%)       | 
|POLY-3 RATE (b)    |        0/12.59          2/14.31          0/10.20          1/13.39          0/12.70          1/12.06         | 
|POLY-3 PERCENT (g) |        0.0%             14.0%            0.0%             7.5%             0.0%             8.3%            | 
|TERMINAL (d)       |        0/9 (0%)         2/12 (17%)       0/8 (0%)         1/12 (8%)        0/11 (0%)        1/10 (10%)      | 
|FIRST INCIDENCE    |        ---              274 (T)          ---              274 (T)          ---              274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.609          P=0.300          (e)              P=0.557          (e)              P=0.521         | 
|POLY 3             |        P=0.623          P=0.261          (e)              P=0.512          (e)              P=0.491         | 
|POLY 1.5           |        P=0.621          P=0.254          (e)              P=0.506          (e)              P=0.497         | 
|POLY 6             |        P=0.622          P=0.267          (e)              P=0.517          (e)              P=0.487         | 
|LOGISTIC REGRESSION|        (e)              P=0.300          (e)              P=0.557          (e)              P=0.521         | 
|COCH-ARM / FISHERS |        P=0.600          P=0.241          (e)              P=0.483          (e)              P=0.500         | 
|ORDER RESTRICTED   |        P=0.329          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Germinal Epithelium                                                                                                      | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                                                                                                             | 
|POLY-3 RATE (b)    |                                                                                                             | 
|POLY-3 PERCENT (g) |                                                                                                             | 
|TERMINAL (d)       |                                                                                                             | 
|FIRST INCIDENCE    |                                                                                                             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                                                                                                             | 
|POLY 3             |                                                                                                             | 
|POLY 1.5           |                                                                                                             | 
|POLY 6             |                                                                                                             | 
|LOGISTIC REGRESSION|                                                                                                             | 
|COCH-ARM / FISHERS |                                                                                                             | 
|ORDER RESTRICTED   |                                                                                                             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 24      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Unilateral                                                                                                               | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        2/15 (13%)       3/15 (20%)       2/14 (14%)       2/15 (13%)       1/15 (7%)       | 
|POLY-3 RATE (b)    |        1/12.63          2/14.31          3/11.17          2/13.43          2/12.70          1/12.06         | 
|POLY-3 PERCENT (g) |        7.9%             14.0%            26.9%            14.9%            15.8%            8.3%            | 
|TERMINAL (d)       |        0/9 (0%)         2/12 (17%)       2/8 (25%)        1/12 (8%)        2/11 (18%)       1/10 (10%)      | 
|FIRST INCIDENCE    |        271              274 (T)          78               271              274 (T)          274 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.386N         P=0.585          P=0.266          P=0.552          P=0.537          P=0.758N        | 
|POLY 3             |        P=0.432N         P=0.544          P=0.249          P=0.522          P=0.502          P=0.752         | 
|POLY 1.5           |        P=0.413N         P=0.533          P=0.268          P=0.510          P=0.501          P=0.758         | 
|POLY 6             |        P=0.448N         P=0.552          P=0.235          P=0.530          P=0.503          P=0.747         | 
|LOGISTIC REGRESSION|        P=0.389N         P=0.559          P=0.321          P=0.530          P=0.502          P=0.755         | 
|COCH-ARM / FISHERS |        P=0.386N         P=0.500          P=0.299          P=0.473          P=0.500          P=0.759N        | 
|ORDER RESTRICTED   |        P=0.520          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Unilateral                                                                                                               | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                                                                                                             | 
|POLY-3 RATE (b)    |                                                                                                             | 
|POLY-3 PERCENT (g) |                                                                                                             | 
|TERMINAL (d)       |                                                                                                             | 
|FIRST INCIDENCE    |                                                                                                             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                                                                                                             | 
|POLY 3             |                                                                                                             | 
|POLY 1.5           |                                                                                                             | 
|POLY 6             |                                                                                                             | 
|LOGISTIC REGRESSION|                                                                                                             | 
|COCH-ARM / FISHERS |                                                                                                             | 
|ORDER RESTRICTED   |                                                                                                             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 25      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Unilateral, Germinal Epithelium                                                                                          | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        2/15 (13%)       4/15 (27%)       2/14 (14%)       3/15 (20%)       3/15 (20%)      | 
|POLY-3 RATE (b)    |        1/12.63          2/14.31          4/11.74          2/13.43          3/13.57          3/12.09         | 
|POLY-3 PERCENT (g) |        7.9%             14.0%            34.1%            14.9%            22.1%            24.8%           | 
|TERMINAL (d)       |        0/9 (0%)         2/12 (17%)       2/8 (25%)        1/12 (8%)        2/11 (18%)       2/10 (20%)      | 
|FIRST INCIDENCE    |        271              274 (T)          78               271              138              271             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.335          P=0.585          P=0.146          P=0.552          P=0.334          P=0.307         | 
|POLY 3             |        P=0.282          P=0.544          P=0.133          P=0.522          P=0.323          P=0.278         | 
|POLY 1.5           |        P=0.305          P=0.533          P=0.143          P=0.510          P=0.315          P=0.289         | 
|POLY 6             |        P=0.265          P=0.552          P=0.129          P=0.530          P=0.329          P=0.269         | 
|LOGISTIC REGRESSION|        P=0.338          P=0.559          P=0.188          P=0.530          P=0.294          P=0.267         | 
|COCH-ARM / FISHERS |        P=0.335          P=0.500          P=0.165          P=0.473          P=0.299          P=0.299         | 
|ORDER RESTRICTED   |        P=0.271          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes: Unilateral, Germinal Epithelium                                                                                          | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                                                                                                             | 
|POLY-3 RATE (b)    |                                                                                                             | 
|POLY-3 PERCENT (g) |                                                                                                             | 
|TERMINAL (d)       |                                                                                                             | 
|FIRST INCIDENCE    |                                                                                                             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                                                                                                             | 
|POLY 3             |                                                                                                             | 
|POLY 1.5           |                                                                                                             | 
|POLY 6             |                                                                                                             | 
|LOGISTIC REGRESSION|                                                                                                             | 
|COCH-ARM / FISHERS |                                                                                                             | 
|ORDER RESTRICTED   |                                                                                                             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 26      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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 Diffuse                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/12 (8%)        0/14 (0%)        1/12 (8%)        0/13 (0%)        4/14 (29%)       0/12 (0%)       | 
|POLY-3 RATE (b)    |        1/11.94          0/13.94          1/10.47          0/12.97          4/14.00          0/11.36         | 
|POLY-3 PERCENT (g) |        8.4%             0.0%             9.6%             0.0%             28.6%            0.0%            | 
|TERMINAL (d)       |        0/9 (0%)         0/12 (0%)        0/8 (0%)         0/12 (0%)        1/11 (9%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        271              ---              150              ---              138              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.510          P=0.469N         P=0.719          P=0.484N         P=0.197          P=0.517N        | 
|POLY 3             |        P=0.490          P=0.469N         P=0.731          P=0.483N         P=0.213          P=0.510N        | 
|POLY 1.5           |        P=0.504          P=0.469N         P=0.741          P=0.484N         P=0.212          P=0.506N        | 
|POLY 6             |        P=0.474          P=0.469N         P=0.724          P=0.483N         P=0.215          P=0.514N        | 
|LOGISTIC REGRESSION|        P=0.526          (e)              P=0.538N         (e)              (e)              P=0.503N        | 
|COCH-ARM / FISHERS |        P=0.522          P=0.462N         P=0.761N         P=0.480N         P=0.213          P=0.500N        | 
|ORDER RESTRICTED   |        P=0.252          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Atrophy Diffuse                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        3/15 (20%)       1/13 (8%)        1/12 (8%)        2/12 (17%)       2/13 (15%)       2/11 (18%)      | 
|POLY-3 RATE (b)    |        3/14.39          1/12.38          1/10.44          2/11.96          2/13.00          2/10.02         | 
|POLY-3 PERCENT (g) |        20.9%            8.1%             9.6%             16.7%            15.4%            20.0%           | 
|TERMINAL (d)       |        0/11 (0%)        0/10 (0%)        0/9 (0%)         0/9 (0%)         0/11 (0%)        0/8 (0%)        | 
|FIRST INCIDENCE    |        109              192              67               165              269              184             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.472          P=0.344N         P=0.403N         P=0.587N         P=0.499N         P=0.641N        | 
|POLY 3             |        P=0.445          P=0.355N         P=0.423N         P=0.588N         P=0.548N         P=0.669N        | 
|POLY 1.5           |        P=0.439          P=0.353N         P=0.417N         P=0.595N         P=0.556N         P=0.670N        | 
|POLY 6             |        P=0.455          P=0.357N         P=0.426N         P=0.582N         P=0.540N         P=0.663N        | 
|LOGISTIC REGRESSION|        P=0.445          P=0.410N         P=0.167N         P=0.585N         P=0.574          P=0.598N        | 
|COCH-ARM / FISHERS |        P=0.447          P=0.356N         P=0.389N         P=0.612N         P=0.572N         P=0.654N        | 
|ORDER RESTRICTED   |        P=0.589N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 27      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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)        |        0/12 (0%)        0/14 (0%)        0/12 (0%)        1/13 (8%)        2/14 (14%)       2/12 (17%)      | 
|POLY-3 RATE (b)    |        0/11.90          0/13.94          0/9.63           1/12.97          2/12.66          2/11.39         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             7.7%             15.8%            17.6%           | 
|TERMINAL (d)       |        0/9 (0%)         0/12 (0%)        0/8 (0%)         1/12 (8%)        2/11 (18%)       1/10 (10%)      | 
|FIRST INCIDENCE    |        ---              ---              ---              274 (T)          274 (T)          271             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.031 *        (e)              (e)              P=0.557          P=0.280          P=0.242         | 
|POLY 3             |        P=0.027 *        (e)              (e)              P=0.517          P=0.243          P=0.218         | 
|POLY 1.5           |        P=0.027 *        (e)              (e)              P=0.517          P=0.251          P=0.222         | 
|POLY 6             |        P=0.026 *        (e)              (e)              P=0.518          P=0.236          P=0.215         | 
|LOGISTIC REGRESSION|        P=0.025 *        (e)              (e)              P=0.557          P=0.280          P=0.217         | 
|COCH-ARM / FISHERS |        P=0.027 *        (e)              (e)              P=0.520          P=0.280          P=0.239         | 
|ORDER RESTRICTED   |        P=0.078          (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)        |        2/15 (13%)       1/13 (8%)        1/12 (8%)        0/12 (0%)        0/13 (0%)        1/11 (9%)       | 
|POLY-3 RATE (b)    |        2/13.08          1/11.72          1/10.03          0/10.47          0/12.88          1/9.26          | 
|POLY-3 PERCENT (g) |        15.3%            8.5%             10.0%            0.0%             0.0%             10.8%           | 
|TERMINAL (d)       |        2/11 (18%)       1/10 (10%)       0/9 (0%)         0/9 (0%)         0/11 (0%)        1/8 (13%)       | 
|FIRST INCIDENCE    |        275 (T)          275 (T)          207              ---              ---              275 (T)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.459N         P=0.535N         P=0.577N         P=0.280N         P=0.234N         P=0.616N        | 
|POLY 3             |        P=0.430N         P=0.539N         P=0.594N         P=0.282N         P=0.233N         P=0.622N        | 
|POLY 1.5           |        P=0.440N         P=0.540N         P=0.602N         P=0.281N         P=0.243N         P=0.622N        | 
|POLY 6             |        P=0.424N         P=0.539N         P=0.580N         P=0.281N         P=0.225N         P=0.618N        | 
|LOGISTIC REGRESSION|        P=0.464N         P=0.535N         P=0.594N         (e)              (e)              P=0.616N        | 
|COCH-ARM / FISHERS |        P=0.465N         P=0.556N         P=0.586N         P=0.299N         P=0.278N         P=0.619N        | 
|ORDER RESTRICTED   |        P=0.265N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 28      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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: Follicle                                                                                                          | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/13 (15%)       0/15 (0%)        0/13 (0%)        0/14 (0%)        0/14 (0%)        0/14 (0%)       | 
|POLY-3 RATE (b)    |        2/12.94          0/14.31          0/10.06          0/13.39          0/12.66          0/11.92         | 
|POLY-3 PERCENT (g) |        15.5%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/9 (0%)         0/12 (0%)        0/8 (0%)         0/12 (0%)        0/11 (0%)        0/10 (0%)       | 
|FIRST INCIDENCE    |        197              ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.217N         P=0.208N         P=0.291N         P=0.216N         P=0.249N         P=0.258N        | 
|POLY 3             |        P=0.166N         P=0.207N         P=0.292N         P=0.222N         P=0.235N         P=0.249N        | 
|POLY 1.5           |        P=0.175N         P=0.203N         P=0.269N         P=0.218N         P=0.227N         P=0.235N        | 
|POLY 6             |        P=0.158N         P=0.210N         P=0.311N         P=0.226N         P=0.242N         P=0.263N        | 
|LOGISTIC REGRESSION|        P=0.183N         P=0.188N         P=0.133N         P=0.216N         P=0.142N         P=0.114N        | 
|COCH-ARM / FISHERS |        P=0.201N         P=0.206N         P=0.240N         P=0.222N         P=0.222N         P=0.222N        | 
|ORDER RESTRICTED   |        P=0.010N*        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        VEHICLE          3125 PPM         6250 PPM         12500            25000            50000           | 
|                   |        CONTROL                                            PPM              PPM              PPM             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: Follicle                                                                                                          | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/15 (7%)        0/13 (0%)        0/12 (0%)        0/15 (0%)        0/14 (0%)        0/11 (0%)       | 
|POLY-3 RATE (b)    |        1/13.39          0/11.67          0/8.84           0/10.85          0/13.80          0/8.74          | 
|POLY-3 PERCENT (g) |        7.5%             0.0%             0.0%             0.0%             0.0%             0.0%            | 
|TERMINAL (d)       |        0/11 (0%)        0/10 (0%)        0/8 (0%)         0/9 (0%)         0/11 (0%)        0/7 (0%)        | 
|FIRST INCIDENCE    |        242              ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.430N         P=0.533N         P=0.573N         P=0.552N         P=0.485N         P=0.573N        | 
|POLY 3             |        P=0.373N         P=0.527N         P=0.581N         P=0.542N         P=0.494N         P=0.584N        | 
|POLY 1.5           |        P=0.392N         P=0.526N         P=0.574N         P=0.528N         P=0.499N         P=0.577N        | 
|POLY 6             |        P=0.355N         P=0.531N         P=0.587N         P=0.550N         P=0.492N         P=0.591N        | 
|LOGISTIC REGRESSION|        P=0.438N         P=0.550N         P=0.544N         P=0.496N         P=0.591N         P=0.555N        | 
|COCH-ARM / FISHERS |        P=0.437N         P=0.536N         P=0.556N         P=0.500N         P=0.517N         P=0.577N        | 
|ORDER RESTRICTED   |        P=0.152N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  03/05/03                           EXPERIMENT: 99033 TEST: 01                                            Page 29      
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC 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)        |        10/15 (67%)      8/13 (62%)       9/13 (69%)       10/12 (83%)      10/14 (71%)      10/14 (71%)     | 
|POLY-3 RATE (b)    |        10/14.06         8/11.67          9/9.84           10/10.33         10/13.85         10/10.84        | 
|POLY-3 PERCENT (g) |        71.1%            68.6%            91.5%            96.8%            72.2%            92.3%           | 
|TERMINAL (d)       |        7/11 (64%)       8/10 (80%)       9/9 (100%)       9/9 (100%)       9/11 (82%)       8/8 (100%)      | 
|FIRST INCIDENCE    |        200              275 (T)          275 (T)          184              270              92              | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.090          P=0.494N         P=0.493          P=0.341          P=0.630N         P=0.231         | 
|POLY 3             |        P=0.201          P=0.613N         P=0.237          P=0.126          P=0.636          P=0.201         | 
|POLY 1.5           |        P=0.256          P=0.568N         P=0.332          P=0.177          P=0.622          P=0.300         | 
|POLY 6             |        P=0.162          P=0.663          P=0.161          P=0.099          P=0.628          P=0.133         | 
|LOGISTIC REGRESSION|        P=0.171          P=0.507N         P=0.361          P=0.173          P=0.664N         P=0.283         | 
|COCH-ARM / FISHERS |        P=0.425          P=0.544N         P=0.604          P=0.298          P=0.550          P=0.550         | 
|ORDER RESTRICTED   |        P=0.104          (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).