National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/6156

TDMS Study 96007-05 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                         TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF)                      DATE: 07/14/03       
EXPERIMENT: 96007 TEST: 05                                                                                     TIME: 14:49:36       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-75411                              ROUTE: GAVAGE                                                  NTP C#: 96007F       
PATHOLOGIST: SELLS, DONALD                                                                                     CAS: 57117-31-4      
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                         31 WEEK SSAC RATS                                                          
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    25017 Scheduled Sacrifice                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     110399 110499                                                                                
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
                                                                                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                         TOXIC EQUIVALENCY FACTOR EVALUATION(PECDF)                      DATE: 07/14/03       
EXPERIMENT: 96007 TEST: 05                                                                                     TIME: 14:49:36       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-75411                              ROUTE: GAVAGE                                                  NTP C#: 96007F       
PATHOLOGIST: SELLS, DONALD                                                                                     CAS: 57117-31-4      
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF       TOXIC EQUIVALENCY FACTOR EVALUATION(                                                                       
===============================================================                                                                     
Female Rats                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Liver                                  Pigmentation                                                                                 
Liver: Hepatocyte                      Hypertrophy                                                                                  
Ovary                                  Atrophy                                                                                      
Thymus                                 Atrophy                                                                                      
Uterus: Endometrium                    Hyperplasia Cystic                                                                           
===============================================================                                                                     
                                                                                                                                   
       Date:  07/14/03                           EXPERIMENT: 96007 TEST: 05                                            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          6 NG/KG          20 NG/KG         44 NG/KG         92 NG/KG         200             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/10 (10%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         2/10 (20%)      | 
|POLY-3 RATE (b)    |        1/1.09           0/0.00           0/0.00           0/0.00           0/0.00           2/2.08          | 
|POLY-3 PERCENT (g) |        92.2%            0.0%             0.0%             0.0%             0.0%             96.4%           | 
|INT SACRIFICE 1 (c)|        1/10 (10%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         2/10 (20%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        211 (I)          ---              ---              ---              ---              211 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.389          P=1.000N         P=1.000N         P=1.000N         P=1.000N         P=0.500         | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              P=0.301         | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              P=0.319         | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              P=0.299         | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.387          P=1.000          P=1.000          P=1.000          P=1.000          P=0.500         | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          6 NG/KG          20 NG/KG         44 NG/KG         92 NG/KG         200             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Basophilic Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/10 (0%)        2/10 (20%)       0/10 (0%)        1/10 (10%)       0/10 (0%)        0/10 (0%)       | 
|POLY-3 RATE (b)    |        0/0.09           2/2.08           0/0.09           1/1.09           0/0.09           0/0.09          | 
|POLY-3 PERCENT (g) |        0.0%             96.4%            0.0%             92.2%            0.0%             0.0%            | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        2/10 (20%)       0/10 (0%)        1/10 (10%)       0/10 (0%)        0/10 (0%)       | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              211 (I)          ---              211 (I)          ---              ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.274N         P=0.234          (e)              P=0.500          (e)              (e)             | 
|POLY 3             |        P=0.143N         P=0.068          (e)              P=0.161          (e)              (e)             | 
|POLY 1.5           |        P=0.151N         P=0.079          (e)              P=0.189          (e)              (e)             | 
|POLY 6             |        P=0.143N         P=0.067          (e)              P=0.159          (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.273N         P=0.237          (e)              P=0.500          (e)              (e)             | 
|ORDER RESTRICTED   |        P=0.521N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  07/14/03                           EXPERIMENT: 96007 TEST: 05                                            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          6 NG/KG          20 NG/KG         44 NG/KG         92 NG/KG         200             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        9/10 (90%)       10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)    | 
|POLY-3 RATE (b)    |        9/9.01           10/10.00         10/10.00         10/10.00         10/10.00         10/10.00        | 
|POLY-3 PERCENT (g) |        99.9%            100.0%           100.0%           100.0%           100.0%           100.0%          | 
|INT SACRIFICE 1 (c)|        9/10 (90%)       10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)    | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        211 (I)          211 (I)          211 (I)          211 (I)          211 (I)          211 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.464          P=0.500          P=0.500          P=0.500          P=0.500          P=0.500         | 
|POLY 3             |        P=0.468          P=0.484          P=0.484          P=0.484          P=0.484          P=0.484         | 
|POLY 1.5           |        P=0.466          P=0.483          P=0.483          P=0.483          P=0.483          P=0.483         | 
|POLY 6             |        P=0.473          P=0.489          P=0.489          P=0.489          P=0.489          P=0.489         | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.463          P=0.500          P=0.500          P=0.500          P=0.500          P=0.500         | 
|ORDER RESTRICTED   |        P=0.055          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          6 NG/KG          20 NG/KG         44 NG/KG         92 NG/KG         200             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Mixed Cell Focus                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/10 (50%)       4/10 (40%)       5/10 (50%)       3/10 (30%)       2/10 (20%)       5/10 (50%)      | 
|POLY-3 RATE (b)    |        5/5.05           4/4.06           5/5.05           3/3.07           2/2.08           5/5.05          | 
|POLY-3 PERCENT (g) |        99.1%            98.6%            99.1%            97.9%            96.4%            99.1%           | 
|INT SACRIFICE 1 (c)|        5/10 (50%)       4/10 (40%)       5/10 (50%)       3/10 (30%)       2/10 (20%)       5/10 (50%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        211 (I)          211 (I)          211 (I)          211 (I)          211 (I)          211 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.569N         P=0.500N         P=0.669          P=0.328N         P=0.180N         P=0.669         | 
|POLY 3             |        P=0.536N         P=0.407N         P=0.586          P=0.235N         P=0.099N         P=0.586         | 
|POLY 1.5           |        P=0.539N         P=0.415N         P=0.593          P=0.243N         P=0.106N         P=0.593         | 
|POLY 6             |        P=0.537N         P=0.407N         P=0.586          P=0.235N         P=0.099N         P=0.586         | 
|LOGISTIC REGRESSION|        (e)              (e)              P=0.673          P=0.324N         (e)              P=0.673         | 
|COCH-ARM / FISHERS |        P=0.569N         P=0.500N         P=0.672N         P=0.325N         P=0.175N         P=0.672N        | 
|ORDER RESTRICTED   |        P=0.337N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  07/14/03                           EXPERIMENT: 96007 TEST: 05                                            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          6 NG/KG          20 NG/KG         44 NG/KG         92 NG/KG         200             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/10 (0%)        1/10 (10%)       3/10 (30%)       4/10 (40%)       7/10 (70%)       8/10 (80%)      | 
|POLY-3 RATE (b)    |        0/0.09           1/1.09           3/3.07           4/4.06           7/7.03           8/8.02          | 
|POLY-3 PERCENT (g) |        0.0%             92.2%            97.9%            98.6%            99.6%            99.8%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        1/10 (10%)       3/10 (30%)       4/10 (40%)       7/10 (70%)       8/10 (80%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              211 (I)          211 (I)          211 (I)          211 (I)          211 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.500          P=0.111          P=0.051          P=0.003 **       P<0.001 **      | 
|POLY 3             |        P<0.001 **       P=0.161          P=0.025 *        P=0.007 **       P<0.001 **       P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       P=0.189          P=0.029 *        P=0.009 **       P<0.001 **       P<0.001 **      | 
|POLY 6             |        P<0.001 **       P=0.159          P=0.025 *        P=0.007 **       P<0.001 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.500          P=0.105          P=0.043 *        P=0.002 **       P<0.001 **      | 
|ORDER RESTRICTED   |        P=0.002 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          6 NG/KG          20 NG/KG         44 NG/KG         92 NG/KG         200             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/10 (0%)        1/10 (10%)       3/10 (30%)       6/10 (60%)       8/10 (80%)       8/10 (80%)      | 
|POLY-3 RATE (b)    |        0/0.09           1/1.09           3/3.07           6/6.04           8/8.02           8/8.02          | 
|POLY-3 PERCENT (g) |        0.0%             92.2%            97.9%            99.4%            99.8%            99.8%           | 
|INT SACRIFICE 1 (c)|        0/10 (0%)        1/10 (10%)       3/10 (30%)       6/10 (60%)       8/10 (80%)       8/10 (80%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        ---              211 (I)          211 (I)          211 (I)          211 (I)          211 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.500          P=0.111          P=0.009 **       P<0.001 **       P<0.001 **      | 
|POLY 3             |        P<0.001 **       P=0.161          P=0.025 *        P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       P=0.189          P=0.029 *        P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 6             |        P<0.001 **       P=0.159          P=0.025 *        P<0.001 **       P<0.001 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              P<0.001 **       P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.500          P=0.105          P=0.005 **       P<0.001 **       P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  07/14/03                           EXPERIMENT: 96007 TEST: 05                                            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          6 NG/KG          20 NG/KG         44 NG/KG         92 NG/KG         200             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/10 (50%)       7/10 (70%)       7/10 (70%)       6/10 (60%)       8/10 (80%)       9/10 (90%)      | 
|POLY-3 RATE (b)    |        5/5.05           7/7.03           7/7.03           6/6.04           8/8.02           9/9.01          | 
|POLY-3 PERCENT (g) |        99.1%            99.6%            99.6%            99.4%            99.8%            99.9%           | 
|INT SACRIFICE 1 (c)|        5/10 (50%)       7/10 (70%)       7/10 (70%)       6/10 (60%)       8/10 (80%)       9/10 (90%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        211 (I)          211 (I)          211 (I)          211 (I)          211 (I)          211 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.057          P=0.328          P=0.328          P=0.500          P=0.180          P=0.077         | 
|POLY 3             |        P=0.055          P=0.265          P=0.265          P=0.424          P=0.130          P=0.040 *       | 
|POLY 1.5           |        P=0.055          P=0.271          P=0.271          P=0.430          P=0.134          P=0.042 *       | 
|POLY 6             |        P=0.056          P=0.266          P=0.266          P=0.425          P=0.131          P=0.041 *       | 
|LOGISTIC REGRESSION|        (e)              P=0.324          P=0.324          (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.055          P=0.325          P=0.325          P=0.500          P=0.175          P=0.070         | 
|ORDER RESTRICTED   |        P=0.046 *        (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          6 NG/KG          20 NG/KG         44 NG/KG         92 NG/KG         200             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Ovary                                                                                                                            | 
|     Cyst                                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/10 (10%)       0/10 (0%)        0/10 (0%)        1/10 (10%)       0/10 (0%)        2/10 (20%)      | 
|POLY-3 RATE (b)    |        1/1.09           0/0.09           0/0.09           1/1.09           0/0.09           2/2.08          | 
|POLY-3 PERCENT (g) |        92.2%            0.0%             0.0%             92.2%            0.0%             96.4%           | 
|INT SACRIFICE 1 (c)|        1/10 (10%)       0/10 (0%)        0/10 (0%)        1/10 (10%)       0/10 (0%)        2/10 (20%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        211 (I)          ---              ---              211 (I)          ---              211 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.136          P=0.500N         P=0.500N         P=0.766          P=0.500N         P=0.500         | 
|POLY 3             |        P=0.074          P=0.161N         P=0.161N         P=0.531          P=0.161N         P=0.301         | 
|POLY 1.5           |        P=0.081          P=0.189N         P=0.189N         P=0.553          P=0.189N         P=0.319         | 
|POLY 6             |        P=0.074          P=0.159N         P=0.159N         P=0.529          P=0.159N         P=0.299         | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.134          P=0.500N         P=0.500N         P=0.763N         P=0.500N         P=0.500         | 
|ORDER RESTRICTED   |        P=0.064          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  07/14/03                           EXPERIMENT: 96007 TEST: 05                                            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          6 NG/KG          20 NG/KG         44 NG/KG         92 NG/KG         200             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        10/10 (100%)     0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         10/10 (100%)    | 
|POLY-3 RATE (b)    |        10/10.00         0/0.00           0/0.00           0/0.00           0/0.00           10/10.00        | 
|POLY-3 PERCENT (g) |        100.0%           0.0%             0.0%             0.0%             0.0%             100.0%          | 
|INT SACRIFICE 1 (c)|        10/10 (100%)     0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         10/10 (100%)    | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        211 (I)          ---              ---              ---              ---              211 (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          6 NG/KG          20 NG/KG         44 NG/KG         92 NG/KG         200             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/10 (10%)       0/10 (0%)        0/10 (0%)        2/10 (20%)       0/10 (0%)        5/10 (50%)      | 
|POLY-3 RATE (b)    |        1/1.09           0/0.09           0/0.09           2/2.08           0/0.09           5/5.05          | 
|POLY-3 PERCENT (g) |        92.2%            0.0%             0.0%             96.4%            0.0%             99.1%           | 
|INT SACRIFICE 1 (c)|        1/10 (10%)       0/10 (0%)        0/10 (0%)        2/10 (20%)       0/10 (0%)        5/10 (50%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        211 (I)          ---              ---              211 (I)          ---              211 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.500N         P=0.500N         P=0.500          P=0.500N         P=0.077         | 
|POLY 3             |        P<0.001 **       P=0.161N         P=0.161N         P=0.301          P=0.161N         P=0.023 *       | 
|POLY 1.5           |        P<0.001 **       P=0.189N         P=0.189N         P=0.319          P=0.189N         P=0.026 *       | 
|POLY 6             |        P<0.001 **       P=0.159N         P=0.159N         P=0.299          P=0.159N         P=0.023 *       | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.500N         P=0.500N         P=0.500          P=0.500N         P=0.070         | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  07/14/03                           EXPERIMENT: 96007 TEST: 05                                            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          6 NG/KG          20 NG/KG         44 NG/KG         92 NG/KG         200             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thyroid Gland: Follicular Cell                                                                                                   | 
|     Hypertrophy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/10 (20%)       1/10 (10%)       5/10 (50%)       3/10 (30%)       2/10 (20%)       2/10 (20%)      | 
|POLY-3 RATE (b)    |        2/2.08           1/1.09           5/5.05           3/3.07           2/2.08           2/2.08          | 
|POLY-3 PERCENT (g) |        96.4%            92.2%            99.1%            97.9%            96.4%            96.4%           | 
|INT SACRIFICE 1 (c)|        2/10 (20%)       1/10 (10%)       5/10 (50%)       3/10 (30%)       2/10 (20%)       2/10 (20%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        211 (I)          211 (I)          211 (I)          211 (I)          211 (I)          211 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.451N         P=0.500N         P=0.180          P=0.500          P=0.707          P=0.707         | 
|POLY 3             |        P=0.379N         P=0.301N         P=0.099          P=0.354          P=0.544          P=0.544         | 
|POLY 1.5           |        P=0.386N         P=0.319N         P=0.106          P=0.367          P=0.559          P=0.559         | 
|POLY 6             |        P=0.378N         P=0.299N         P=0.099          P=0.353          P=0.543          P=0.543         | 
|LOGISTIC REGRESSION|        P=0.451N         (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.451N         P=0.500N         P=0.175          P=0.500          P=0.709N         P=0.709N        | 
|ORDER RESTRICTED   |        P=0.360          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        0 NG/KG          6 NG/KG          20 NG/KG         44 NG/KG         92 NG/KG         200             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus                                                                                                                           | 
|     Metaplasia                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/10 (50%)       6/10 (60%)       3/10 (30%)       5/10 (50%)       6/10 (60%)       3/10 (30%)      | 
|POLY-3 RATE (b)    |        5/5.05           6/6.04           3/3.07           5/5.05           6/6.04           3/3.07          | 
|POLY-3 PERCENT (g) |        99.1%            99.4%            97.9%            99.1%            99.4%            97.9%           | 
|INT SACRIFICE 1 (c)|        5/10 (50%)       6/10 (60%)       3/10 (30%)       5/10 (50%)       6/10 (60%)       3/10 (30%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        211 (I)          211 (I)          211 (I)          211 (I)          211 (I)          211 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.268N         P=0.500          P=0.328N         P=0.669          P=0.500          P=0.328N        | 
|POLY 3             |        P=0.225N         P=0.424          P=0.235N         P=0.586          P=0.424          P=0.235N        | 
|POLY 1.5           |        P=0.226N         P=0.430          P=0.243N         P=0.593          P=0.430          P=0.243N        | 
|POLY 6             |        P=0.226N         P=0.425          P=0.235N         P=0.586          P=0.425          P=0.235N        | 
|LOGISTIC REGRESSION|        P=0.267N         (e)              P=0.324N         P=0.673          (e)              P=0.324N        | 
|COCH-ARM / FISHERS |        P=0.267N         P=0.500          P=0.325N         P=0.672N         P=0.500          P=0.325N        | 
|ORDER RESTRICTED   |        P=0.225N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  07/14/03                           EXPERIMENT: 96007 TEST: 05                                            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          6 NG/KG          20 NG/KG         44 NG/KG         92 NG/KG         200             | 
|                   |                                                                                             NG/KG           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus: Endometrium                                                                                                              | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/10 (40%)       2/10 (20%)       4/10 (40%)       6/10 (60%)       7/10 (70%)       8/10 (80%)      | 
|POLY-3 RATE (b)    |        4/4.06           2/2.08           4/4.06           6/6.04           7/7.03           8/8.02          | 
|POLY-3 PERCENT (g) |        98.6%            96.4%            98.6%            99.4%            99.6%            99.8%           | 
|INT SACRIFICE 1 (c)|        4/10 (40%)       2/10 (20%)       4/10 (40%)       6/10 (60%)       7/10 (70%)       8/10 (80%)      | 
|TERMINAL (d)       |        0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)        | 
|FIRST INCIDENCE    |        211 (I)          211 (I)          211 (I)          211 (I)          211 (I)          211 (I)         | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.006 **       P=0.317N         P=0.672          P=0.331          P=0.190          P=0.091         | 
|POLY 3             |        P=0.004 **       P=0.204N         P=0.571          P=0.254          P=0.131          P=0.048 *       | 
|POLY 1.5           |        P=0.004 **       P=0.214N         P=0.579N         P=0.261          P=0.136          P=0.051         | 
|POLY 6             |        P=0.004 **       P=0.203N         P=0.571          P=0.255          P=0.131          P=0.048 *       | 
|LOGISTIC REGRESSION|        (e)              (e)              P=0.676N         P=0.327          (e)              P=0.085         | 
|COCH-ARM / FISHERS |        P=0.006 **       P=0.314N         P=0.675N         P=0.328          P=0.185          P=0.085         | 
|ORDER RESTRICTED   |        P=0.008 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
(a)  Number of tumor-bearing animals /  number of animals examined at site.                                                         
(b)  Number of tumor-bearing animals / Poly-3 number                                                                                
(d)  Observed incidence at terminal kill.                                                                                           
(f)  Beneath the control incidence are the P-values associated with the trend                                                       
test.  Beneath the dosed group incidence are the P-values corresponding to                                                          
pairwise comparisons between the controls and that dosed group.  The life                                                           
table analysis regards tumors in animals dying prior to  terminal kill as                                                           
 being (directly or indirectly) the cause of death.                                                                                 
Logistic regression is an alternative                                                                                               
 method for analyzing the incidence of non-fatal tumors. The Cochran-Armitage                                                       
and Fishers exact tests compare directly the overall incidence rates                                                                
For all tests a negative trend is indicated by N                                                                                    
(e)  Value of Statistic cannot be computed.                                                                                         
(g)  Poly-3 adjusted lifetime tumor incidence.                                                                                      
(I)  Interim sacrifice                                                                                                              
(T)  Terminal sacrifice                                                                                                             
#   Tumor rates based on number of animals necropsied.                                                                              
*   To the right of any statistical result, indicates significance at (P<=0.05).                                                    
**  To the right of any statistical result, indicates significance at (P<=0.01).                                                    
NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.