https://ntp.niehs.nih.gov/go/5288

TDMS Study 96007-03 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                         TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD)                      DATE: 11/25/02       
EXPERIMENT: 96007 TEST: 03                                                                                     TIME: 12:14:20       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-75411                              ROUTE: GAVAGE                                                  NTP C#: 96007G       
PATHOLOGIST: SELLS, DONALD                                                                                     CAS: 1746-01-6       
------------------------------------------------------------------------------------------------------------------------------------
                                                            53 WEEK SSAC                                                            
               REASONS FOR REMOVAL:    25017 Scheduled Sacrifice                                                                    
               REMOVAL DATE RANGE:     060399 060499                                                                                
               TREATMENT GROUPS:       INCLUDE 001    0 NG/KG                                                                       
                                       INCLUDE 002    3 NG/KG                                                                       
                                       INCLUDE 003    10 NG/KG                                                                      
                                       INCLUDE 004    22 NG/KG                                                                      
                                       INCLUDE 005    46 NG/KG                                                                      
                                       INCLUDE 006    100     NG/KG                                                                 
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                         TOXIC EQUIVALENCY FACTOR EVALUATION (TCDD)                      DATE: 11/25/02       
EXPERIMENT: 96007 TEST: 03                                                                                     TIME: 12:14:20       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-75411                              ROUTE: GAVAGE                                                  NTP C#: 96007G       
PATHOLOGIST: SELLS, DONALD                                                                                     CAS: 1746-01-6       
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF       TOXIC EQUIVALENCY FACTOR EVALUATION                                                                        
===============================================================                                                                     
Female Rats                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Adrenal Cortex                         Hyperplasia                                                                                  
Liver                                  Basophilic Focus                                                                             
                                       Fatty Change Diffuse                                                                         
                                       Mixed Cell Focus                                                                             
                                       Pigmentation                                                                                 
                                       Toxic Hepatopathy                                                                            
Liver: Bile Duct                       Fibrosis                                                                                     
                                       Hyperplasia                                                                                  
Liver: Hepatocyte                      Hypertrophy                                                                                  
                                       Multinucleated                                                                               
Mammary Gland                          Cyst                                                                                         
Pancreas                               Inflammation Chronic                                                                         
Pancreas: Acinus                       Atrophy                                                                                      
                                       Vacuolization Cytoplasmic                                                                    
Thymus                                 Atrophy                                                                                      
Thyroid Gland: Follicular Cell         Hypertrophy                                                                                  
Uterus                                 Metaplasia                                                                                   
===============================================================                                                                     
       Date:  11/25/02                           EXPERIMENT: 96007 TEST: 03                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions in        Rats(SPRAGUE-DAWLEY)  -        TOXIC EQUIVALENCY FACTOR EVALUATION         
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Degeneration Cystic                                                                                                         | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/8 (13%)        1/8 (13%)        1/8 (13%)        2/8 (25%)        0/8 (0%)         1/8 (13%)       | 
|POLY-3 RATE (b)    |        1/1.35           1/1.35           1/1.35           2/2.30           0/0.40           1/1.35          | 
|POLY-3 PERCENT (g) |        74.1%            74.1%            74.1%            87.0%            0.0%             74.1%           | 
|INT SACRIFICE 1 (c)|        1/8 (12.5%)      1/8 (12.5%)      1/8 (12.5%)      2/8 (25%)        0/8 (0%)         1/8 (12.5%)     | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        368 (I)          368 (I)          368 (I)          368 (I)          ---              368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.515N         P=0.768          P=0.768          P=0.500          P=0.500N         P=0.768         | 
|POLY 3             |        P=0.413N         P=0.548          P=0.548          P=0.314          P=0.174N         P=0.548         | 
|POLY 1.5           |        P=0.431N         P=0.590          P=0.590          P=0.348          P=0.229N         P=0.590         | 
|POLY 6             |        P=0.409N         P=0.536          P=0.536          P=0.304          P=0.159N         P=0.536         | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.515N         P=0.767N         P=0.767N         P=0.500          P=0.500N         P=0.767N        | 
|ORDER RESTRICTED   |        P=0.435N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/8 (13%)        0/8 (0%)         0/8 (0%)         0/8 (0%)         3/8 (38%)        2/8 (25%)       | 
|POLY-3 RATE (b)    |        1/1.35           0/0.40           0/0.40           0/0.40           3/3.25           2/2.30          | 
|POLY-3 PERCENT (g) |        74.1%            0.0%             0.0%             0.0%             92.3%            87.0%           | 
|INT SACRIFICE 1 (c)|        1/8 (12.5%)      0/8 (0%)         0/8 (0%)         0/8 (0%)         3/8 (37.5%)      2/8 (25%)       | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        368 (I)          ---              ---              ---              368 (I)          368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.053          P=0.500N         P=0.500N         P=0.500N         P=0.288          P=0.500         | 
|POLY 3             |        P=0.026 *        P=0.174N         P=0.174N         P=0.174N         P=0.156          P=0.314         | 
|POLY 1.5           |        P=0.029 *        P=0.229N         P=0.229N         P=0.229N         P=0.180          P=0.348         | 
|POLY 6             |        P=0.026 *        P=0.159N         P=0.159N         P=0.159N         P=0.149          P=0.304         | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.051          P=0.500N         P=0.500N         P=0.500N         P=0.285          P=0.500         | 
|ORDER RESTRICTED   |        P=0.017 *        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  11/25/02                           EXPERIMENT: 96007 TEST: 03                                            Page 2       
Statistical Analysis of Non-neoplastic Lesions in       Rats(SPRAGUE-DAWLEY)  -        TOXIC EQUIVALENCY FACTOR EVALUATION          
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/8 (63%)        3/8 (38%)        4/8 (50%)        4/8 (50%)        5/8 (63%)        7/8 (88%)       | 
|POLY-3 RATE (b)    |        5/5.15           3/3.25           4/4.20           4/4.20           5/5.15           7/7.05          | 
|POLY-3 PERCENT (g) |        97.1%            92.3%            95.2%            95.2%            97.1%            99.3%           | 
|INT SACRIFICE 1 (c)|        5/8 (62.5%)      3/8 (37.5%)      4/8 (50%)        4/8 (50%)        5/8 (62.5%)      7/8 (87.5%)     | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        368 (I)          368 (I)          368 (I)          368 (I)          368 (I)          368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.052          P=0.314N         P=0.500N         P=0.500N         P=0.691          P=0.288         | 
|POLY 3             |        P=0.050          P=0.231N         P=0.420N         P=0.420N         P=0.623          P=0.237         | 
|POLY 1.5           |        P=0.051          P=0.247N         P=0.435N         P=0.435N         P=0.635          P=0.247         | 
|POLY 6             |        P=0.050          P=0.227N         P=0.417N         P=0.417N         P=0.621          P=0.235         | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.050          P=0.310N         P=0.500N         P=0.500N         P=0.696N         P=0.285         | 
|ORDER RESTRICTED   |        P=0.123          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Basophilic Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/8 (0%)         1/8 (13%)        1/8 (13%)        0/8 (0%)         0/8 (0%)         3/8 (38%)       | 
|POLY-3 RATE (b)    |        0/0.40           1/1.35           1/1.35           0/0.40           0/0.40           3/3.25          | 
|POLY-3 PERCENT (g) |        0.0%             74.1%            74.1%            0.0%             0.0%             92.3%           | 
|INT SACRIFICE 1 (c)|        0/8 (0%)         1/8 (12.5%)      1/8 (12.5%)      0/8 (0%)         0/8 (0%)         3/8 (37.5%)     | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              368 (I)          368 (I)          ---              ---              368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.035 *        P=0.500          P=0.500          (e)              (e)              P=0.107         | 
|POLY 3             |        P=0.014 *        P=0.174          P=0.174          (e)              (e)              P=0.022 *       | 
|POLY 1.5           |        P=0.018 *        P=0.229          P=0.229          (e)              (e)              P=0.031 *       | 
|POLY 6             |        P=0.013 *        P=0.159          P=0.159          (e)              (e)              P=0.020 *       | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.033 *        P=0.500          P=0.500          (e)              (e)              P=0.100         | 
|ORDER RESTRICTED   |        P=0.160          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  11/25/02                           EXPERIMENT: 96007 TEST: 03                                            Page 3       
Statistical Analysis of Non-neoplastic Lesions in       Rats(SPRAGUE-DAWLEY)  -        TOXIC EQUIVALENCY FACTOR EVALUATION          
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Clear Cell Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/8 (25%)        0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)        | 
|POLY-3 RATE (b)    |        2/2.30           0/0.40           0/0.40           0/0.40           0/0.40           0/0.40          | 
|POLY-3 PERCENT (g) |        87.0%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|INT SACRIFICE 1 (c)|        2/8 (25%)        0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)        | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        368 (I)          ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.247N         P=0.232N         P=0.232N         P=0.232N         P=0.232N         P=0.232N        | 
|POLY 3             |        P=0.097N         P=0.069N         P=0.069N         P=0.069N         P=0.069N         P=0.069N        | 
|POLY 1.5           |        P=0.116N         P=0.093N         P=0.093N         P=0.093N         P=0.093N         P=0.093N        | 
|POLY 6             |        P=0.092N         P=0.064N         P=0.064N         P=0.064N         P=0.064N         P=0.064N        | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.244N         P=0.233N         P=0.233N         P=0.233N         P=0.233N         P=0.233N        | 
|ORDER RESTRICTED   |        P=0.217N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Fatty Change Diffuse                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         2/8 (25%)        6/8 (75%)       | 
|POLY-3 RATE (b)    |        0/0.40           0/0.40           0/0.40           0/0.40           2/2.30           6/6.10          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             87.0%            98.4%           | 
|INT SACRIFICE 1 (c)|        0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         2/8 (25%)        6/8 (75%)       | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              368 (I)          368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              (e)              P=0.232          P=0.006 **      | 
|POLY 3             |        P<0.001 **       (e)              (e)              (e)              P=0.069          P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              (e)              P=0.093          P<0.001 **      | 
|POLY 6             |        P<0.001 **       (e)              (e)              (e)              P=0.064          P<0.001 **      | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              (e)              P=0.233          P=0.003 **      | 
|ORDER RESTRICTED   |        P=0.020 *        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  11/25/02                           EXPERIMENT: 96007 TEST: 03                                            Page 4       
Statistical Analysis of Non-neoplastic Lesions in       Rats(SPRAGUE-DAWLEY)  -        TOXIC EQUIVALENCY FACTOR EVALUATION          
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        8/8 (100%)       8/8 (100%)       8/8 (100%)       8/8 (100%)       8/8 (100%)       8/8 (100%)      | 
|POLY-3 RATE (b)    |        8/8.00           8/8.00           8/8.00           8/8.00           8/8.00           8/8.00          | 
|POLY-3 PERCENT (g) |        100.0%           100.0%           100.0%           100.0%           100.0%           100.0%          | 
|INT SACRIFICE 1 (c)|        8/8 (100%)       8/8 (100%)       8/8 (100%)       8/8 (100%)       8/8 (100%)       8/8 (100%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        368 (I)          368 (I)          368 (I)          368 (I)          368 (I)          368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Mixed Cell Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/8 (25%)        5/8 (63%)        0/8 (0%)         6/8 (75%)        7/8 (88%)        8/8 (100%)      | 
|POLY-3 RATE (b)    |        2/2.30           5/5.15           0/0.40           6/6.10           7/7.05           8/8.00          | 
|POLY-3 PERCENT (g) |        87.0%            97.1%            0.0%             98.4%            99.3%            100.0%          | 
|INT SACRIFICE 1 (c)|        2/8 (25%)        5/8 (62.5%)      0/8 (0%)         6/8 (75%)        7/8 (87.5%)      8/8 (100%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        368 (I)          368 (I)          ---              368 (I)          368 (I)          368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.165          P=0.232N         P=0.073          P=0.025 *        P=0.006 **      | 
|POLY 3             |        P<0.001 **       P=0.089          P=0.069N         P=0.024 *        P=0.002 **       P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       P=0.101          P=0.093N         P=0.029 *        P=0.003 **       P<0.001 **      | 
|POLY 6             |        P<0.001 **       P=0.085          P=0.064N         P=0.023 *        P=0.002 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.157          P=0.233N         P=0.066          P=0.020 *        P=0.003 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  11/25/02                           EXPERIMENT: 96007 TEST: 03                                            Page 5       
Statistical Analysis of Non-neoplastic Lesions in       Rats(SPRAGUE-DAWLEY)  -        TOXIC EQUIVALENCY FACTOR EVALUATION          
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/8 (0%)         0/8 (0%)         5/8 (63%)        8/8 (100%)       8/8 (100%)       8/8 (100%)      | 
|POLY-3 RATE (b)    |        0/0.40           0/0.40           5/5.15           8/8.00           8/8.00           8/8.00          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             97.1%            100.0%           100.0%           100.0%          | 
|INT SACRIFICE 1 (c)|        0/8 (0%)         0/8 (0%)         5/8 (62.5%)      8/8 (100%)       8/8 (100%)       8/8 (100%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              368 (I)          368 (I)          368 (I)          368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              P=0.018 *        P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 3             |        P<0.001 **       (e)              P<0.001 **       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 1.5           |        P<0.001 **       (e)              P<0.001 **       P<0.001N**       P<0.001N**       P<0.001N**      | 
|POLY 6             |        P<0.001 **       (e)              P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              P=0.013 *        P<0.001 **       P<0.001 **       P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Toxic Hepatopathy                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/8 (0%)         0/8 (0%)         1/8 (13%)        0/8 (0%)         6/8 (75%)        8/8 (100%)      | 
|POLY-3 RATE (b)    |        0/0.40           0/0.40           1/1.35           0/0.40           6/6.10           8/8.00          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             74.1%            0.0%             98.4%            100.0%          | 
|INT SACRIFICE 1 (c)|        0/8 (0%)         0/8 (0%)         1/8 (12.5%)      0/8 (0%)         6/8 (75%)        8/8 (100%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              368 (I)          ---              368 (I)          368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              P=0.500          (e)              P=0.006 **       P<0.001 **      | 
|POLY 3             |        P<0.001 **       (e)              P=0.174          (e)              P<0.001 **       P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       (e)              P=0.229          (e)              P<0.001 **       P<0.001 **      | 
|POLY 6             |        P<0.001 **       (e)              P=0.159          (e)              P<0.001 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              P=0.500          (e)              P=0.003 **       P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  11/25/02                           EXPERIMENT: 96007 TEST: 03                                            Page 6       
Statistical Analysis of Non-neoplastic Lesions in       Rats(SPRAGUE-DAWLEY)  -        TOXIC EQUIVALENCY FACTOR EVALUATION          
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Bile Duct                                                                                                                 | 
|     Fibrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         1/8 (13%)        2/8 (25%)       | 
|POLY-3 RATE (b)    |        0/0.40           0/0.40           0/0.40           0/0.40           1/1.35           2/2.30          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             74.1%            87.0%           | 
|INT SACRIFICE 1 (c)|        0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         1/8 (12.5%)      2/8 (25%)       | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              368 (I)          368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.015 *        (e)              (e)              (e)              P=0.500          P=0.232         | 
|POLY 3             |        P=0.004 **       (e)              (e)              (e)              P=0.174          P=0.069         | 
|POLY 1.5           |        P=0.006 **       (e)              (e)              (e)              P=0.229          P=0.093         | 
|POLY 6             |        P=0.004 **       (e)              (e)              (e)              P=0.159          P=0.064         | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.014 *        (e)              (e)              (e)              P=0.500          P=0.233         | 
|ORDER RESTRICTED   |        P=0.232          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Bile Duct                                                                                                                 | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/8 (0%)         0/8 (0%)         1/8 (13%)        2/8 (25%)        3/8 (38%)        8/8 (100%)      | 
|POLY-3 RATE (b)    |        0/0.40           0/0.40           1/1.35           2/2.30           3/3.25           8/8.00          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             74.1%            87.0%            92.3%            100.0%          | 
|INT SACRIFICE 1 (c)|        0/8 (0%)         0/8 (0%)         1/8 (12.5%)      2/8 (25%)        3/8 (37.5%)      8/8 (100%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              368 (I)          368 (I)          368 (I)          368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              P=0.500          P=0.232          P=0.107          P<0.001 **      | 
|POLY 3             |        P<0.001 **       (e)              P=0.174          P=0.069          P=0.022 *        P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       (e)              P=0.229          P=0.093          P=0.031 *        P<0.001 **      | 
|POLY 6             |        P<0.001 **       (e)              P=0.159          P=0.064          P=0.020 *        P<0.001 **      | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              P=0.500          P=0.233          P=0.100          P<0.001 **      | 
|ORDER RESTRICTED   |        P=0.002 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  11/25/02                           EXPERIMENT: 96007 TEST: 03                                            Page 7       
Statistical Analysis of Non-neoplastic Lesions in       Rats(SPRAGUE-DAWLEY)  -        TOXIC EQUIVALENCY FACTOR EVALUATION          
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/8 (0%)         4/8 (50%)        7/8 (88%)        8/8 (100%)       8/8 (100%)       8/8 (100%)      | 
|POLY-3 RATE (b)    |        0/0.40           4/4.20           7/7.05           8/8.00           8/8.00           8/8.00          | 
|POLY-3 PERCENT (g) |        0.0%             95.2%            99.3%            100.0%           100.0%           100.0%          | 
|INT SACRIFICE 1 (c)|        0/8 (0%)         4/8 (50%)        7/8 (87.5%)      8/8 (100%)       8/8 (100%)       8/8 (100%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              368 (I)          368 (I)          368 (I)          368 (I)          368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.047 *        P=0.002 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 3             |        P<0.001 **       P=0.005 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       P=0.007 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 6             |        P<0.001 **       P=0.004 **       P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.038 *        P<0.001 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Multinucleated                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         2/8 (25%)        8/8 (100%)      | 
|POLY-3 RATE (b)    |        0/0.40           0/0.40           0/0.40           0/0.40           2/2.30           8/8.00          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             87.0%            100.0%          | 
|INT SACRIFICE 1 (c)|        0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         2/8 (25%)        8/8 (100%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              368 (I)          368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              (e)              P=0.232          P<0.001 **      | 
|POLY 3             |        P<0.001 **       (e)              (e)              (e)              P=0.069          P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              (e)              P=0.093          P<0.001 **      | 
|POLY 6             |        P<0.001 **       (e)              (e)              (e)              P=0.064          P<0.001 **      | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              (e)              P=0.233          P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  11/25/02                           EXPERIMENT: 96007 TEST: 03                                            Page 8       
Statistical Analysis of Non-neoplastic Lesions in       Rats(SPRAGUE-DAWLEY)  -        TOXIC EQUIVALENCY FACTOR EVALUATION          
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Infiltration Cellular Histiocyte                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        3/8 (38%)        1/8 (13%)        2/8 (25%)        1/8 (13%)        4/8 (50%)        3/8 (38%)       | 
|POLY-3 RATE (b)    |        3/3.25           1/1.35           2/2.30           1/1.35           4/4.20           3/3.25          | 
|POLY-3 PERCENT (g) |        92.3%            74.1%            87.0%            74.1%            95.2%            92.3%           | 
|INT SACRIFICE 1 (c)|        3/8 (37.5%)      1/8 (12.5%)      2/8 (25%)        1/8 (12.5%)      4/8 (50%)        3/8 (37.5%)     | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        368 (I)          368 (I)          368 (I)          368 (I)          368 (I)          368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.236          P=0.288N         P=0.500N         P=0.288N         P=0.500          P=0.691         | 
|POLY 3             |        P=0.195          P=0.156N         P=0.366N         P=0.156N         P=0.398          P=0.578         | 
|POLY 1.5           |        P=0.202          P=0.180N         P=0.391N         P=0.180N         P=0.417          P=0.599         | 
|POLY 6             |        P=0.193          P=0.149N         P=0.360N         P=0.149N         P=0.393          P=0.573         | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.233          P=0.285N         P=0.500N         P=0.285N         P=0.500          P=0.696N        | 
|ORDER RESTRICTED   |        P=0.262          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mammary Gland                                                                                                                    | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        3/8 (38%)        0/2 (0%)         0/2 (0%)         0/0 (0%)         0/0 (0%)         0/8 (0%)        | 
|POLY-3 RATE (b)    |        3/3.25           0/0.10           0/0.10           0/0.00           0/0.00           0/0.40          | 
|POLY-3 PERCENT (g) |        92.3%            0.0%             0.0%             0.0%             0.0%             0.0%            | 
|INT SACRIFICE 1 (c)|        3/8 (37.5%)      0/2 (0%)         0/2 (0%)         0/0 (0%)         0/0 (0%)         0/8 (0%)        | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        368 (I)          ---              ---              ---              ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.109N         P=0.435N         P=0.435N         P=1.000N         P=1.000N         P=0.107N        | 
|POLY 3             |        (e)              P=0.174N         P=0.174N         (e)              (e)              P=0.022N*       | 
|POLY 1.5           |        (e)              P=0.216N         P=0.216N         (e)              (e)              P=0.031N*       | 
|POLY 6             |        (e)              P=0.164N         P=0.164N         (e)              (e)              P=0.020N*       | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.103N         P=0.467N         P=0.467N         P=1.000          P=1.000          P=0.100N        | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  11/25/02                           EXPERIMENT: 96007 TEST: 03                                            Page 9       
Statistical Analysis of Non-neoplastic Lesions in       Rats(SPRAGUE-DAWLEY)  -        TOXIC EQUIVALENCY FACTOR EVALUATION          
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        8/8 (100%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         5/7 (71%)       | 
|POLY-3 RATE (b)    |        8/8.00           0/0.00           0/0.00           0/0.00           0/0.00           5/5.10          | 
|POLY-3 PERCENT (g) |        100.0%           0.0%             0.0%             0.0%             0.0%             98.0%           | 
|INT SACRIFICE 1 (c)|        8/8 (100%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         5/7 (71.4%)     | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        368 (I)          ---              ---              ---              ---              368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.121N         (e)              (e)              (e)              (e)              P=0.202N        | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              P=0.153N        | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              P=0.160N        | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              P=0.152N        | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.113N         (e)              (e)              (e)              (e)              P=0.200N        | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas                                                                                                                         | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         2/8 (25%)       | 
|POLY-3 RATE (b)    |        0/0.40           0/0.40           0/0.40           0/0.40           0/0.40           2/2.30          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             87.0%           | 
|INT SACRIFICE 1 (c)|        0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         2/8 (25%)       | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.010 *        (e)              (e)              (e)              (e)              P=0.232         | 
|POLY 3             |        P<0.001 **       (e)              (e)              (e)              (e)              P=0.069         | 
|POLY 1.5           |        P=0.002 **       (e)              (e)              (e)              (e)              P=0.093         | 
|POLY 6             |        P<0.001 **       (e)              (e)              (e)              (e)              P=0.064         | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.010 *        (e)              (e)              (e)              (e)              P=0.233         | 
|ORDER RESTRICTED   |        P=0.217          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  11/25/02                           EXPERIMENT: 96007 TEST: 03                                            Page 10      
Statistical Analysis of Non-neoplastic Lesions in       Rats(SPRAGUE-DAWLEY)  -        TOXIC EQUIVALENCY FACTOR EVALUATION          
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas: Acinus                                                                                                                 | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         2/8 (25%)       | 
|POLY-3 RATE (b)    |        0/0.40           0/0.40           0/0.40           0/0.40           0/0.40           2/2.30          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             87.0%           | 
|INT SACRIFICE 1 (c)|        0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         2/8 (25%)       | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.010 *        (e)              (e)              (e)              (e)              P=0.232         | 
|POLY 3             |        P<0.001 **       (e)              (e)              (e)              (e)              P=0.069         | 
|POLY 1.5           |        P=0.002 **       (e)              (e)              (e)              (e)              P=0.093         | 
|POLY 6             |        P<0.001 **       (e)              (e)              (e)              (e)              P=0.064         | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.010 *        (e)              (e)              (e)              (e)              P=0.233         | 
|ORDER RESTRICTED   |        P=0.217          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Pancreas: Acinus                                                                                                                 | 
|     Vacuolization Cytoplasmic                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         7/8 (88%)       | 
|POLY-3 RATE (b)    |        0/0.40           0/0.40           0/0.40           0/0.40           0/0.40           7/7.05          | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             0.0%             99.3%           | 
|INT SACRIFICE 1 (c)|        0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         0/8 (0%)         7/8 (87.5%)     | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              ---              368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              (e)              (e)              P=0.002 **      | 
|POLY 3             |        P<0.001 **       (e)              (e)              (e)              (e)              P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              (e)              (e)              P<0.001 **      | 
|POLY 6             |        P<0.001 **       (e)              (e)              (e)              (e)              P<0.001 **      | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              (e)              (e)              P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  11/25/02                           EXPERIMENT: 96007 TEST: 03                                            Page 11      
Statistical Analysis of Non-neoplastic Lesions in       Rats(SPRAGUE-DAWLEY)  -        TOXIC EQUIVALENCY FACTOR EVALUATION          
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        8/8 (100%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         8/8 (100%)      | 
|POLY-3 RATE (b)    |        8/8.00           0/0.00           0/0.00           0/0.00           0/0.00           8/8.00          | 
|POLY-3 PERCENT (g) |        100.0%           0.0%             0.0%             0.0%             0.0%             100.0%          | 
|INT SACRIFICE 1 (c)|        8/8 (100%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         8/8 (100%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        368 (I)          ---              ---              ---              ---              368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/8 (50%)        2/8 (25%)        3/7 (43%)        7/8 (88%)        8/8 (100%)       8/8 (100%)      | 
|POLY-3 RATE (b)    |        4/4.20           2/2.30           3/3.20           7/7.05           8/8.00           8/8.00          | 
|POLY-3 PERCENT (g) |        95.2%            87.0%            93.8%            99.3%            100.0%           100.0%          | 
|INT SACRIFICE 1 (c)|        4/8 (50%)        2/8 (25%)        3/7 (42.9%)      7/8 (87.5%)      8/8 (100%)       8/8 (100%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        368 (I)          368 (I)          368 (I)          368 (I)          368 (I)          368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.309N         P=0.592N         P=0.148          P=0.047 *        P=0.047 *       | 
|POLY 3             |        P<0.001 **       P=0.204N         P=0.491N         P=0.095          P=0.013 *        P=0.013 *       | 
|POLY 1.5           |        P<0.001 **       P=0.224N         P=0.509N         P=0.103          P=0.015 *        P=0.015 *       | 
|POLY 6             |        P<0.001 **       P=0.199N         P=0.487N         P=0.093          P=0.013 *        P=0.013 *       | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.304N         P=0.595N         P=0.141          P=0.038 *        P=0.038 *       | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  11/25/02                           EXPERIMENT: 96007 TEST: 03                                            Page 12      
Statistical Analysis of Non-neoplastic Lesions in       Rats(SPRAGUE-DAWLEY)  -        TOXIC EQUIVALENCY FACTOR EVALUATION          
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: Follicular Cell                                                                                                   | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/8 (0%)         1/8 (13%)        2/8 (25%)        2/8 (25%)        3/8 (38%)        5/8 (63%)       | 
|POLY-3 RATE (b)    |        0/0.40           1/1.35           2/2.30           2/2.30           3/3.25           5/5.15          | 
|POLY-3 PERCENT (g) |        0.0%             74.1%            87.0%            87.0%            92.3%            97.1%           | 
|INT SACRIFICE 1 (c)|        0/8 (0%)         1/8 (12.5%)      2/8 (25%)        2/8 (25%)        3/8 (37.5%)      5/8 (62.5%)     | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              368 (I)          368 (I)          368 (I)          368 (I)          368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.004 **       P=0.500          P=0.232          P=0.232          P=0.107          P=0.018 *       | 
|POLY 3             |        P=0.002 **       P=0.174          P=0.069          P=0.069          P=0.022 *        P<0.001 **      | 
|POLY 1.5           |        P=0.002 **       P=0.229          P=0.093          P=0.093          P=0.031 *        P<0.001 **      | 
|POLY 6             |        P=0.002 **       P=0.159          P=0.064          P=0.064          P=0.020 *        P<0.001 **      | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.004 **       P=0.500          P=0.233          P=0.233          P=0.100          P=0.013 *       | 
|ORDER RESTRICTED   |        P=0.035 *        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Metaplasia                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        7/8 (88%)        0/0 (0%)         0/0 (0%)         0/1 (0%)         0/0 (0%)         4/8 (50%)       | 
|POLY-3 RATE (b)    |        7/7.05           0/0.00           0/0.00           0/0.05           0/0.00           4/4.20          | 
|POLY-3 PERCENT (g) |        99.3%            0.0%             0.0%             0.0%             0.0%             95.2%           | 
|INT SACRIFICE 1 (c)|        7/8 (87.5%)      0/0 (0%)         0/0 (0%)         0/1 (0%)         0/0 (0%)         4/8 (50%)       | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        368 (I)          ---              ---              ---              ---              368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.146N         P=1.000N         P=1.000N         P=0.252N         P=1.000          P=0.148N        | 
|POLY 3             |        (e)              (e)              (e)              P=0.012N*        (e)              P=0.095N        | 
|POLY 1.5           |        (e)              (e)              (e)              P=0.023N*        (e)              P=0.103N        | 
|POLY 6             |        (e)              (e)              (e)              P=0.010N*        (e)              P=0.093N        | 
|LOGISTIC REGRESSION|        P=0.138N         (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.138N         P=1.000          P=1.000          P=0.222N         P=1.000          P=0.141N        | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
       Date:  11/25/02                           EXPERIMENT: 96007 TEST: 03                                            Page 13      
Statistical Analysis of Non-neoplastic Lesions in       Rats(SPRAGUE-DAWLEY)  -        TOXIC EQUIVALENCY FACTOR EVALUATION          
                                         Terminal Sacrifice at 143 weeks                                                            
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          3 NG/KG          10 NG/KG         22 NG/KG         46 NG/KG         100             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus: Endometrium                                                                                                              | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/8 (63%)        0/0 (0%)         0/0 (0%)         1/1 (100%)       0/0 (0%)         2/8 (25%)       | 
|POLY-3 RATE (b)    |        5/5.15           0/0.00           0/0.00           1/1.00           0/0.00           2/2.30          | 
|POLY-3 PERCENT (g) |        97.1%            0.0%             0.0%             100.0%           0.0%             87.0%           | 
|INT SACRIFICE 1 (c)|        5/8 (62.5%)      0/0 (0%)         0/0 (0%)         1/1 (100%)       0/0 (0%)         2/8 (25%)       | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        368 (I)          ---              ---              368 (I)          ---              368 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.092N         P=1.000          P=1.000          P=0.638          P=1.000N         P=0.165N        | 
|POLY 3             |        (e)              (e)              (e)              P=0.603          (e)              P=0.089N        | 
|POLY 1.5           |        (e)              (e)              (e)              P=0.612          (e)              P=0.101N        | 
|POLY 6             |        (e)              (e)              (e)              P=0.602          (e)              P=0.085N        | 
|LOGISTIC REGRESSION|        P=0.086N         (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.086N         P=1.000          P=1.000          P=0.667          P=1.000          P=0.157N        | 
|ORDER RESTRICTED   |        (e)              (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).