National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/14519

TDMS Study 99039-01 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: BIORELIANCE                                     TRANSGENIC MODEL EVALUATION II                            DATE: 02/21/03       
EXPERIMENT: 99039 TEST: 01                                                                                     TIME: 10:25:14       
TEST TYPE:  26-39 WEEKS                         CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-75408                              ROUTE: DOSED FEED                                              NTP C#: C99039       
PATHOLOGIST: LANNING, LYNDA                                                                                    CAS: 55589-62-3      
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                         FINAL#3/TG.AC MICE                                                         
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE 001    VEHICLE CONTROL                                                               
                                       INCLUDE 002    0.3%                                                                          
                                       INCLUDE 003    1.0 %                                                                         
                                       INCLUDE 004    3.0 %                                                                         
                                       INCLUDE 006    VEHICLE CONTROL                                                               
                                       INCLUDE 007    0.3 %                                                                         
                                       INCLUDE 008    1.0%                                                                          
                                       INCLUDE 009    3.0%                                                                          
                                                                                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: BIORELIANCE                                     TRANSGENIC MODEL EVALUATION II                            DATE: 02/21/03       
EXPERIMENT: 99039 TEST: 01                                                                                     TIME: 10:25:14       
TEST TYPE:  26-39 WEEKS                         CAGES FROM 0000 TO LAST CAGE                                                        
CONT: NO1-ES-75408                              ROUTE: DOSED FEED                                              NTP C#: C99039       
PATHOLOGIST: LANNING, LYNDA                                                                                    CAS: 55589-62-3      
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF             TRANSGENIC MODEL EVALUATION II                                                                       
===============================================================                                                                     
Male Mice                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Spleen                                 Hematopoietic Cell Proliferation                                                             
===============================================================                                                                     
Female Mice                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Mesentery: Fat                         Necrosis Focal                                                                               
Uterus: Endometrium                    Hyperplasia Cystic                                                                           
===============================================================                                                                     
                                                                                                                                   
       Date:  02/21/03                           EXPERIMENT: 99039 TEST: 01                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions in        Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -              TRANSGENIC MODEL EVALUA
TION II                                                                                                                             
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     VEHICLE      0.3%         1.0 %        3.0 %       |VEHICLE      0.3 %        1.0%         3.0%         | 
|                   |     CONTROL                                            |CONTROL                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     10/14 (71%)  0/0 (0%)     0/0 (0%)     11/15 (73%) |0/14 (0%)    0/1 (0%)     0/0 (0%)     0/15 (0%)    | 
|POLY-3 RATE (b)    |     10/12.35     0/0.00       0/0.00       11/15.00    |0/13.31      0/0.02       0/0.00       0/13.60      | 
|POLY-3 PERCENT (g) |     81.0%        0.0%         0.0%         73.3%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     10/12 (83%)  0/0 (0%)     0/0 (0%)     10/14 (71%) |0/12 (0%)    0/0 (0%)     0/0 (0%)     0/12 (0%)    | 
|FIRST INCIDENCE    |     274 (T)      ---          ---          172         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.558N     P=1.000      P=1.000      P=0.565N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     (e)          (e)          (e)          P=0.493N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     (e)          (e)          (e)          P=0.563N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     (e)          (e)          (e)          P=0.450N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.556N     (e)          (e)          P=0.614N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.565      P=1.000      P=1.000      P=0.617     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     VEHICLE      0.3%         1.0 %        3.0 %       |VEHICLE      0.3 %        1.0%         3.0%         | 
|                   |     CONTROL                                            |CONTROL                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex                                                                                                                   | 
|     Hypertrophy Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     9/14 (64%)   0/0 (0%)     0/0 (0%)     5/15 (33%)  |0/14 (0%)    0/1 (0%)     0/0 (0%)     0/15 (0%)    | 
|POLY-3 RATE (b)    |     9/13.16      0/0.00       0/0.00       5/14.25     |0/13.31      0/0.02       0/0.00       0/13.60      | 
|POLY-3 PERCENT (g) |     68.4%        0.0%         0.0%         35.1%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     8/12 (67%)   0/0 (0%)     0/0 (0%)     5/14 (36%)  |0/12 (0%)    0/0 (0%)     0/0 (0%)     0/12 (0%)    | 
|FIRST INCIDENCE    |     157          ---          ---          274 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.066N     P=0.515N     P=0.486N     P=0.073N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     (e)          (e)          (e)          P=0.081N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     (e)          (e)          (e)          P=0.083N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     (e)          (e)          (e)          P=0.082N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.064N     (e)          (e)          P=0.082N    |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.078N     P=1.000      P=1.000      P=0.097N    |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/21/03                           EXPERIMENT: 99039 TEST: 01                                            Page 2       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -              TRANSGENIC MODEL EVALUAT
ION II                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     VEHICLE      0.3%         1.0 %        3.0 %       |VEHICLE      0.3 %        1.0%         3.0%         | 
|                   |     CONTROL                                            |CONTROL                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex: Subcapsular                                                                                                      | 
|     Hyperplasia Focal                                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/14 (0%)    0/0 (0%)     0/0 (0%)     0/15 (0%)   |9/14 (64%)   0/1 (0%)     0/0 (0%)     6/15 (40%)   | 
|POLY-3 RATE (b)    |     0/12.35      0/0.00       0/0.00       0/14.25     |9/13.64      0/0.02       0/0.00       6/13.99      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |66.0%        0.0%         0.0%         42.9%        | 
|TERMINAL (d)       |     0/12 (0%)    0/0 (0%)     0/0 (0%)     0/14 (0%)   |8/12 (67%)   0/0 (0%)     0/0 (0%)     5/12 (42%)   | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |240          ---          ---          232          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.257N     P=0.500N     P=0.500N     P=0.243N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |(e)          P=0.846N     (e)          P=0.201N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |(e)          P=0.800N     (e)          P=0.194N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |(e)          P=0.857N     (e)          P=0.202N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.174N     (e)          (e)          P=0.201N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.186N     P=0.400N     P=1.000      P=0.175N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     VEHICLE      0.3%         1.0 %        3.0 %       |VEHICLE      0.3 %        1.0%         3.0%         | 
|                   |     CONTROL                                            |CONTROL                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Adrenal Cortex: Zona Reticularis                                                                                                 | 
|     Vacuolization Cytoplasmic                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/14 (0%)    0/0 (0%)     0/0 (0%)     0/15 (0%)   |9/14 (64%)   0/1 (0%)     0/0 (0%)     10/15 (67%)  | 
|POLY-3 RATE (b)    |     0/12.35      0/0.00       0/0.00       0/14.25     |9/13.67      0/0.02       0/0.00       10/13.60     | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |65.8%        0.0%         0.0%         73.5%        | 
|TERMINAL (d)       |     0/12 (0%)    0/0 (0%)     0/0 (0%)     0/14 (0%)   |8/12 (67%)   0/0 (0%)     0/0 (0%)     10/12 (83%)  | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |236          ---          ---          274 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.392      P=0.515N     P=0.515N     P=0.494      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |(e)          P=0.845N     (e)          P=0.491      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |(e)          P=0.799N     (e)          P=0.531      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |(e)          P=0.856N     (e)          P=0.451      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.471      (e)          (e)          P=0.528      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.469      P=0.400N     P=1.000      P=0.600      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/21/03                           EXPERIMENT: 99039 TEST: 01                                            Page 3       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -              TRANSGENIC MODEL EVALUAT
ION II                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     VEHICLE      0.3%         1.0 %        3.0 %       |VEHICLE      0.3 %        1.0%         3.0%         | 
|                   |     CONTROL                                            |CONTROL                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Eye: Retina                                                                                                                      | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     15/15 (100%) 0/0 (0%)     0/0 (0%)     14/15 (93%) |13/13 (100%) 0/0 (0%)     0/0 (0%)     14/14 (100%) | 
|POLY-3 RATE (b)    |     15/15.00     0/0.00       0/0.00       14/15.00    |13/13.00     0/0.00       0/0.00       14/14.00     | 
|POLY-3 PERCENT (g) |     100.0%       0.0%         0.0%         93.3%       |100.0%       0.0%         0.0%         100.0%       | 
|TERMINAL (d)       |     13/13 (100%) 0/0 (0%)     0/0 (0%)     13/14 (93%) |12/12 (100%) 0/0 (0%)     0/0 (0%)     12/12 (100%) | 
|FIRST INCIDENCE    |     148          ---          ---          172         |240          ---          ---          156          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.370N     (e)          (e)          P=0.296N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     (e)          (e)          (e)          P=0.500N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     (e)          (e)          (e)          P=0.500N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     (e)          (e)          (e)          P=0.500N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.367N     (e)          (e)          P=0.500N    |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     VEHICLE      0.3%         1.0 %        3.0 %       |VEHICLE      0.3 %        1.0%         3.0%         | 
|                   |     CONTROL                                            |CONTROL                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Dilatation Focal                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/1 (0%)     0/0 (0%)     2/15 (13%)  |0/15 (0%)    0/1 (0%)     0/0 (0%)     1/15 (7%)    | 
|POLY-3 RATE (b)    |     0/13.35      0/0.97       0/0.00       2/14.25     |0/13.86      0/0.02       0/0.00       1/13.60      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         14.0%       |0.0%         0.0%         0.0%         7.4%         | 
|TERMINAL (d)       |     0/13 (0%)    0/0 (0%)     0/0 (0%)     2/14 (14%)  |0/12 (0%)    0/0 (0%)     0/0 (0%)     1/12 (8%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          274 (T)     |---          ---          ---          274 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.182      (e)          (e)          P=0.252     |P=0.369      (e)          (e)          P=0.500      | 
|POLY 3             |     (e)          (e)          (e)          P=0.246     |(e)          (e)          (e)          P=0.496      | 
|POLY 1.5           |     (e)          (e)          (e)          P=0.242     |(e)          (e)          (e)          P=0.496      | 
|POLY 6             |     (e)          (e)          (e)          P=0.248     |(e)          (e)          (e)          P=0.498      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          P=0.252     |(e)          (e)          (e)          P=0.500      | 
|COCH-ARM / FISHERS |     P=0.154      (e)          (e)          P=0.241     |P=0.357      (e)          (e)          P=0.500      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/21/03                           EXPERIMENT: 99039 TEST: 01                                            Page 4       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -              TRANSGENIC MODEL EVALUAT
ION II                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     VEHICLE      0.3%         1.0 %        3.0 %       |VEHICLE      0.3 %        1.0%         3.0%         | 
|                   |     CONTROL                                            |CONTROL                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    0/0 (0%)     0/1 (0%)     0/15 (0%)   |2/15 (13%)   0/2 (0%)     0/0 (0%)     3/15 (20%)   | 
|POLY-3 RATE (b)    |     1/14.16      0/0.00       0/0.34       0/14.25     |2/13.86      0/0.39       0/0.00       3/14.41      | 
|POLY-3 PERCENT (g) |     7.1%         0.0%         0.0%         0.0%        |14.4%        0.0%         0.0%         20.8%        | 
|TERMINAL (d)       |     0/13 (0%)    0/0 (0%)     0/0 (0%)     0/14 (0%)   |2/12 (17%)   0/0 (0%)     0/0 (0%)     2/12 (17%)   | 
|FIRST INCIDENCE    |     157          ---          ---          ---         |274 (T)      ---          ---          156          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.459N     P=0.515N     P=0.486N     P=0.486N    |P=0.382      P=1.000      P=1.000      P=0.500      | 
|POLY 3             |     (e)          (e)          P=0.970N     P=0.499N    |(e)          P=0.831N     (e)          P=0.519      | 
|POLY 1.5           |     (e)          (e)          P=0.967N     P=0.499N    |(e)          P=0.808N     (e)          P=0.510      | 
|POLY 6             |     (e)          (e)          P=0.973N     P=0.499N    |(e)          P=0.847N     (e)          P=0.530      | 
|LOGISTIC REGRESSION|     P=0.739N     (e)          P=0.972N     P=0.861N    |P=0.373      (e)          (e)          P=0.558      | 
|COCH-ARM / FISHERS |     P=0.370N     P=1.000      P=0.937N     P=0.500N    |P=0.387      P=0.772N     P=1.000      P=0.500      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     VEHICLE      0.3%         1.0 %        3.0 %       |VEHICLE      0.3 %        1.0%         3.0%         | 
|                   |     CONTROL                                            |CONTROL                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver: Hepatocyte                                                                                                                | 
|     Necrosis Focal                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/15 (7%)    0/0 (0%)     0/1 (0%)     0/15 (0%)   |2/15 (13%)   0/2 (0%)     0/0 (0%)     3/15 (20%)   | 
|POLY-3 RATE (b)    |     1/13.35      0/0.00       0/0.34       0/14.25     |2/13.86      0/0.39       0/0.00       3/13.60      | 
|POLY-3 PERCENT (g) |     7.5%         0.0%         0.0%         0.0%        |14.4%        0.0%         0.0%         22.1%        | 
|TERMINAL (d)       |     1/13 (8%)    0/0 (0%)     0/0 (0%)     0/14 (0%)   |2/12 (17%)   0/0 (0%)     0/0 (0%)     3/12 (25%)   | 
|FIRST INCIDENCE    |     274 (T)      ---          ---          ---         |274 (T)      ---          ---          274 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.355N     P=1.000      P=1.000      P=0.485N    |P=0.435      P=1.000      P=1.000      P=0.500      | 
|POLY 3             |     (e)          (e)          P=0.970N     P=0.487N    |(e)          P=0.831N     (e)          P=0.491      | 
|POLY 1.5           |     (e)          (e)          P=0.967N     P=0.491N    |(e)          P=0.808N     (e)          P=0.492      | 
|POLY 6             |     (e)          (e)          P=0.973N     P=0.485N    |(e)          P=0.847N     (e)          P=0.496      | 
|LOGISTIC REGRESSION|     P=0.355N     (e)          (e)          (e)         |P=0.435      (e)          (e)          P=0.500      | 
|COCH-ARM / FISHERS |     P=0.370N     P=1.000      P=0.937N     P=0.500N    |P=0.387      P=0.772N     P=1.000      P=0.500      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/21/03                           EXPERIMENT: 99039 TEST: 01                                            Page 5       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -              TRANSGENIC MODEL EVALUAT
ION II                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     VEHICLE      0.3%         1.0 %        3.0 %       |VEHICLE      0.3 %        1.0%         3.0%         | 
|                   |     CONTROL                                            |CONTROL                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lymph Node, Mandibular                                                                                                           | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/14 (14%)   0/0 (0%)     0/0 (0%)     2/15 (13%)  |1/12 (8%)    0/1 (0%)     0/0 (0%)     3/15 (20%)   | 
|POLY-3 RATE (b)    |     2/13.16      0/0.00       0/0.00       2/14.25     |1/11.67      0/0.02       0/0.00       3/14.81      | 
|POLY-3 PERCENT (g) |     15.2%        0.0%         0.0%         14.0%       |8.6%         0.0%         0.0%         20.3%        | 
|TERMINAL (d)       |     1/12 (8%)    0/0 (0%)     0/0 (0%)     2/14 (14%)  |0/10 (0%)    0/0 (0%)     0/0 (0%)     1/12 (8%)    | 
|FIRST INCIDENCE    |     157          ---          ---          274 (T)     |236          ---          ---          156          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.637      P=0.515N     P=0.486N     P=0.648N    |P=0.111      P=0.515N     P=0.515N     P=0.324      | 
|POLY 3             |     (e)          (e)          (e)          P=0.670N    |(e)          P=0.958N     (e)          P=0.389      | 
|POLY 1.5           |     (e)          (e)          (e)          P=0.670N    |(e)          P=0.956N     (e)          P=0.387      | 
|POLY 6             |     (e)          (e)          (e)          P=0.671N    |(e)          P=0.959N     (e)          P=0.393      | 
|LOGISTIC REGRESSION|     P=0.609      (e)          (e)          P=0.679     |P=0.227      (e)          (e)          P=0.439      | 
|COCH-ARM / FISHERS |     P=0.612N     P=1.000      P=1.000      P=0.674N    |P=0.289      P=0.923N     P=1.000      P=0.389      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     VEHICLE      0.3%         1.0 %        3.0 %       |VEHICLE      0.3 %        1.0%         3.0%         | 
|                   |     CONTROL                                            |CONTROL                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Mesentery: Fat                                                                                                                   | 
|     Necrosis Focal                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/2 (100%)   0/0 (0%)     0/0 (0%)     2/2 (100%)  |2/2 (100%)   0/0 (0%)     0/1 (0%)     0/0 (0%)     | 
|POLY-3 RATE (b)    |     2/2.00       0/0.00       0/0.00       2/2.00      |2/2.00       0/0.00       0/0.96       0/0.00       | 
|POLY-3 PERCENT (g) |     100.0%       0.0%         0.0%         100.0%      |100.0%       0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     2/2 (100%)   0/0 (0%)     0/0 (0%)     2/2 (100%)  |2/2 (100%)   0/0 (0%)     0/0 (0%)     0/0 (0%)     | 
|FIRST INCIDENCE    |     274 (T)      ---          ---          274 (T)     |274 (T)      ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=1.000N     (e)          P=1.000      (e)          | 
|POLY 3             |     (e)          (e)          (e)          (e)         |(e)          (e)          P<0.001N**   (e)          | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |(e)          (e)          P<0.001N**   (e)          | 
|POLY 6             |     (e)          (e)          (e)          (e)         |(e)          (e)          P=1.000N     (e)          | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=1.000N     (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.807N     (e)          P=0.333N     (e)          | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/21/03                           EXPERIMENT: 99039 TEST: 01                                            Page 6       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -              TRANSGENIC MODEL EVALUAT
ION II                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     VEHICLE      0.3%         1.0 %        3.0 %       |VEHICLE      0.3 %        1.0%         3.0%         | 
|                   |     CONTROL                                            |CONTROL                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Hematopoietic Cell Proliferation                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     10/15 (67%)  1/1 (100%)   0/1 (0%)     7/15 (47%)  |12/15 (80%)  0/0 (0%)     3/3 (100%)   13/15 (87%)  | 
|POLY-3 RATE (b)    |     10/13.35     1/1.00       0/0.34       7/14.25     |12/14.19     0/0.00       3/3.00       13/14.81     | 
|POLY-3 PERCENT (g) |     74.9%        100.0%       0.0%         49.1%       |84.6%        0.0%         100.0%       87.8%        | 
|TERMINAL (d)       |     10/13 (77%)  0/0 (0%)     0/0 (0%)     7/14 (50%)  |11/12 (92%)  0/0 (0%)     2/2 (100%)   11/12 (92%)  | 
|FIRST INCIDENCE    |     274 (T)      271          ---          274 (T)     |240          ---          270          156          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.095N     P=0.484      P=1.000      P=0.152N    |P=0.305      P=0.500N     P=0.684      P=0.500      | 
|POLY 3             |     P=0.098N     P=0.750      P=0.732N     P=0.155N    |(e)          (e)          P=0.597      P=0.618      | 
|POLY 1.5           |     P=0.120N     P=0.722      P=0.589N     P=0.175N    |(e)          (e)          P=0.549      P=0.563      | 
|POLY 6             |     P=0.087N     P=0.764      P=0.846N     P=0.147N    |(e)          (e)          P=0.677      P=0.697      | 
|LOGISTIC REGRESSION|     P=0.095N     P=0.735      (e)          P=0.152N    |P=0.403      (e)          P=0.783      P=0.452      | 
|COCH-ARM / FISHERS |     P=0.182N     P=0.688      P=0.375N     P=0.231N    |P=0.463      P=1.000      P=0.558      P=0.500      | 
|ORDER RESTRICTED   |     P=0.019N*    (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     VEHICLE      0.3%         1.0 %        3.0 %       |VEHICLE      0.3 %        1.0%         3.0%         | 
|                   |     CONTROL                                            |CONTROL                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Spleen                                                                                                                           | 
|     Pigmentation                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/15 (0%)    0/1 (0%)     0/1 (0%)     0/15 (0%)   |3/15 (20%)   0/0 (0%)     0/3 (0%)     2/15 (13%)   | 
|POLY-3 RATE (b)    |     0/13.35      0/0.97       0/0.34       0/14.25     |3/13.86      0/0.00       0/2.96       2/13.60      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |21.7%        0.0%         0.0%         14.7%        | 
|TERMINAL (d)       |     0/13 (0%)    0/0 (0%)     0/0 (0%)     0/14 (0%)   |3/12 (25%)   0/0 (0%)     0/2 (0%)     2/12 (17%)   | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |274 (T)      ---          ---          274 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.459N     P=1.000      P=0.551N     P=0.500N     | 
|POLY 3             |     (e)          (e)          (e)          (e)         |(e)          (e)          P=0.482N     P=0.509N     | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |(e)          (e)          P=0.490N     P=0.508N     | 
|POLY 6             |     (e)          (e)          (e)          (e)         |(e)          (e)          P=0.471N     P=0.504N     | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.459N     (e)          (e)          P=0.500N     | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.463N     P=1.000      P=0.558N     P=0.500N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/21/03                           EXPERIMENT: 99039 TEST: 01                                            Page 7       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -              TRANSGENIC MODEL EVALUAT
ION II                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     VEHICLE      0.3%         1.0 %        3.0 %       |VEHICLE      0.3 %        1.0%         3.0%         | 
|                   |     CONTROL                                            |CONTROL                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Atrophy Diffuse                                                                                                             | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/15 (20%)   0/0 (0%)     0/0 (0%)     2/14 (14%)  |1/11 (9%)    0/1 (0%)     0/0 (0%)     1/14 (7%)    | 
|POLY-3 RATE (b)    |     3/15.00      0/0.00       0/0.00       2/13.25     |1/11.00      0/0.02       0/0.00       1/13.61      | 
|POLY-3 PERCENT (g) |     20.0%        0.0%         0.0%         15.1%       |9.1%         0.0%         0.0%         7.4%         | 
|TERMINAL (d)       |     1/13 (8%)    0/0 (0%)     0/0 (0%)     2/13 (15%)  |0/10 (0%)    0/0 (0%)     0/0 (0%)     0/12 (0%)    | 
|FIRST INCIDENCE    |     148          ---          ---          274 (T)     |240          ---          ---          156          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.537N     P=0.264N     P=0.232N     P=0.494N    |P=0.542      P=0.516N     P=0.516N     P=0.759      | 
|POLY 3             |     (e)          (e)          (e)          P=0.559N    |(e)          P=0.951N     (e)          P=0.713N     | 
|POLY 1.5           |     (e)          (e)          (e)          P=0.550N    |(e)          P=0.949N     (e)          P=0.710N     | 
|POLY 6             |     (e)          (e)          (e)          P=0.565N    |(e)          P=0.951N     (e)          P=0.717N     | 
|LOGISTIC REGRESSION|     P=0.613N     (e)          (e)          P=0.683N    |P=0.684      (e)          (e)          P=0.367N     | 
|COCH-ARM / FISHERS |     P=0.468N     P=1.000      P=1.000      P=0.535N    |P=0.644N     P=0.917N     P=1.000      P=0.697N     | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     VEHICLE      0.3%         1.0 %        3.0 %       |VEHICLE      0.3 %        1.0%         3.0%         | 
|                   |     CONTROL                                            |CONTROL                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Thymus                                                                                                                           | 
|     Atrophy Focal                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/15 (13%)   0/0 (0%)     0/0 (0%)     0/14 (0%)   |0/11 (0%)    0/1 (0%)     0/0 (0%)     0/14 (0%)    | 
|POLY-3 RATE (b)    |     2/13.35      0/0.00       0/0.00       0/13.25     |0/10.67      0/0.02       0/0.00       0/12.79      | 
|POLY-3 PERCENT (g) |     15.0%        0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     2/13 (15%)   0/0 (0%)     0/0 (0%)     0/13 (0%)   |0/10 (0%)    0/0 (0%)     0/0 (0%)     0/12 (0%)    | 
|FIRST INCIDENCE    |     274 (T)      ---          ---          ---         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.168N     P=1.000N     P=1.000      P=0.235N    |(e)          (e)          (e)          (e)          | 
|POLY 3             |     (e)          (e)          (e)          P=0.232N    |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     (e)          (e)          (e)          P=0.236N    |(e)          (e)          (e)          (e)          | 
|POLY 6             |     (e)          (e)          (e)          P=0.230N    |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.168N     (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.177N     P=1.000      P=1.000      P=0.259N    |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  02/21/03                           EXPERIMENT: 99039 TEST: 01                                            Page 8       
Statistical Analysis of Non-neoplastic Lesions in       Mice(TG.AC HETEROZYGOUS TRANSGENIC)  -              TRANSGENIC MODEL EVALUAT
ION II                                                                                                                              
                                         Terminal Sacrifice at 40 weeks                                                             
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     VEHICLE      0.3%         1.0 %        3.0 %       |VEHICLE      0.3 %        1.0%         3.0%         | 
|                   |     CONTROL                                            |CONTROL                                             | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Uterus: Endometrium                                                                                                              | 
|     Hyperplasia Cystic                                                                                                          | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |                                                        |7/13 (54%)   2/2 (100%)   1/1 (100%)   10/14 (71%)  | 
|POLY-3 RATE (b)    |                                                        |7/12.67      2/2.00       1/1.00       10/13.19     | 
|POLY-3 PERCENT (g) |                                                        |55.2%        100.0%       100.0%       75.9%        | 
|TERMINAL (d)       |                                                        |7/12 (58%)   2/2 (100%)   1/1 (100%)   9/12 (75%)   | 
|FIRST INCIDENCE    |                                                        |274 (T)      274 (T)      274 (T)      232          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |                                                        |P=0.207      P=0.371      P=0.594      P=0.222      | 
|POLY 3             |                                                        |P=0.285      P=0.334      P=0.569      P=0.245      | 
|POLY 1.5           |                                                        |P=0.298      P=0.329      P=0.564      P=0.256      | 
|POLY 6             |                                                        |P=0.290      P=0.343      P=0.578      P=0.250      | 
|LOGISTIC REGRESSION|                                                        |P=0.233      P=0.371      P=0.594      P=0.207      | 
|COCH-ARM / FISHERS |                                                        |P=0.342      P=0.343      P=0.571      P=0.293      | 
|ORDER RESTRICTED   |                                                        |P=0.044 *    (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.