NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                            ACETAMINOPHEN (4-HYDROXYACETANILIDE)                         DATE: 08/18/04       
EXPERIMENT: 55801 TEST: 06                                                                                     TIME: 10:43:19       
TEST TYPE:  ACUTE                               CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: N01-ES-65406                              ROUTE: GAVAGE                                                  NTP C#: 55801E       
PATHOLOGIST: MISSING                                                                                           CAS: 103-90-2        
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                     FINAL #1 RATS/48 HOURS DAY                                                     
                                                                                                                                    
                                                                                                                                    
               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE 004    0 MG/KG 48 HR                                                                 
                                       INCLUDE 008    50 MG/KG48 HR                                                                 
                                       INCLUDE 012    150MG/KG48 HR                                                                 
                                       INCLUDE 016    1500MG/K48 HR                                                                 
                                       INCLUDE 020    2000MG/K48 HR                                                                 
                                                                                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                            ACETAMINOPHEN (4-HYDROXYACETANILIDE)                         DATE: 08/18/04       
EXPERIMENT: 55801 TEST: 06                                                                                     TIME: 10:43:19       
TEST TYPE:  ACUTE                               CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-65406                              ROUTE: GAVAGE                                                  NTP C#: 55801E       
PATHOLOGIST: MISSING                                                                                           CAS: 103-90-2        
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF          ACETAMINOPHEN (4-HYDROXYACETANILI                                                                       
===============================================================                                                                     
Male Rats                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Liver, Left Lobe: Centrilobular        Infiltration Cellular Mononuclear Cell                                                       
                                       Necrosis                                                                                     
Liver, Left Lobe: Hepatocyte           Degeneration                                                                                 
                                       Regeneration                                                                                 
Liver, Left Lobe: Sinusoid             Congestion                                                                                   
Liver, Median Lobe: Centrilobular      Infiltration Cellular Mononuclear Cell                                                       
                                       Necrosis                                                                                     
Liver, Median Lobe: Hepatocyte         Degeneration                                                                                 
                                       Regeneration                                                                                 
Liver, Median Lobe: Sinusoid           Congestion                                                                                   
===============================================================                                                                     
                                                                                                                                   
       Date:  08/18/04                           EXPERIMENT: 55801 TEST: 06                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions in        Rats(FISCHER 344)  -           ACETAMINOPHEN (4-HYDROXYACETANILI           
                                         Terminal Sacrifice at 1 weeks                                                              
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          50 MG/KG         150MG/KG         1500MG/K         2000MG/K                         | 
|                   |        48 HR            48 HR            48 HR            48 HR            48 HR                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver, Left Lobe: Centrilobular                                                                                                  | 
|     Infiltration Cellular Mononuclear Cell                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/6 (0%)         0/6 (0%)         0/6 (0%)         6/6 (100%)       6/6 (100%)                       | 
|POLY-3 RATE (b)    |        0/6.00           0/6.00           0/6.00           6/6.00           6/6.00                           | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             100.0%           100.0%                           | 
|TERMINAL (d)       |        0/6 (0%)         0/6 (0%)         0/6 (0%)         6/6 (100%)       6/6 (100%)                       | 
|FIRST INCIDENCE    |        ---              ---              ---              3 (T)            3 (T)                            | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.003 **       P=0.003 **                       | 
|POLY 3             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 6             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.003 **       P=0.003 **                       | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          50 MG/KG         150MG/KG         1500MG/K         2000MG/K                         | 
|                   |        48 HR            48 HR            48 HR            48 HR            48 HR                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver, Left Lobe: Centrilobular                                                                                                  | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/6 (0%)         0/6 (0%)         0/6 (0%)         6/6 (100%)       6/6 (100%)                       | 
|POLY-3 RATE (b)    |        0/6.00           0/6.00           0/6.00           6/6.00           6/6.00                           | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             100.0%           100.0%                           | 
|TERMINAL (d)       |        0/6 (0%)         0/6 (0%)         0/6 (0%)         6/6 (100%)       6/6 (100%)                       | 
|FIRST INCIDENCE    |        ---              ---              ---              3 (T)            3 (T)                            | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.003 **       P=0.003 **                       | 
|POLY 3             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 6             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.003 **       P=0.003 **                       | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  08/18/04                           EXPERIMENT: 55801 TEST: 06                                            Page 2       
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -           ACETAMINOPHEN (4-HYDROXYACETANILI            
                                         Terminal Sacrifice at 1 weeks                                                              
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          50 MG/KG         150MG/KG         1500MG/K         2000MG/K                         | 
|                   |        48 HR            48 HR            48 HR            48 HR            48 HR                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver, Left Lobe: Hepatocyte                                                                                                     | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/6 (0%)         0/6 (0%)         0/6 (0%)         4/6 (67%)        3/6 (50%)                        | 
|POLY-3 RATE (b)    |        0/6.00           0/6.00           0/6.00           4/6.00           3/6.00                           | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             66.7%            50.0%                            | 
|TERMINAL (d)       |        0/6 (0%)         0/6 (0%)         0/6 (0%)         4/6 (67%)        3/6 (50%)                        | 
|FIRST INCIDENCE    |        ---              ---              ---              3 (T)            3 (T)                            | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.039 *        P=0.101                          | 
|POLY 3             |        P<0.001 **       (e)              (e)              P=0.009 **       P=0.068                          | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P=0.009 **       P=0.068                          | 
|POLY 6             |        P<0.001 **       (e)              (e)              P=0.009 **       P=0.068                          | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.039 *        P=0.101                          | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P=0.030 *        P=0.091                          | 
|ORDER RESTRICTED   |        P=0.002 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          50 MG/KG         150MG/KG         1500MG/K         2000MG/K                         | 
|                   |        48 HR            48 HR            48 HR            48 HR            48 HR                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver, Left Lobe: Hepatocyte                                                                                                     | 
|     Regeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/6 (0%)         0/6 (0%)         0/6 (0%)         5/6 (83%)        6/6 (100%)                       | 
|POLY-3 RATE (b)    |        0/6.00           0/6.00           0/6.00           5/6.00           6/6.00                           | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             83.3%            100.0%                           | 
|TERMINAL (d)       |        0/6 (0%)         0/6 (0%)         0/6 (0%)         5/6 (83%)        6/6 (100%)                       | 
|FIRST INCIDENCE    |        ---              ---              ---              3 (T)            3 (T)                            | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.012 *        P=0.003 **                       | 
|POLY 3             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 6             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.012 *        P=0.003 **                       | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P=0.008 **       P<0.001 **                       | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  08/18/04                           EXPERIMENT: 55801 TEST: 06                                            Page 3       
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -           ACETAMINOPHEN (4-HYDROXYACETANILI            
                                         Terminal Sacrifice at 1 weeks                                                              
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          50 MG/KG         150MG/KG         1500MG/K         2000MG/K                         | 
|                   |        48 HR            48 HR            48 HR            48 HR            48 HR                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver, Left Lobe: Sinusoid                                                                                                       | 
|     Congestion                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/6 (0%)         0/6 (0%)         0/6 (0%)         2/6 (33%)        3/6 (50%)                        | 
|POLY-3 RATE (b)    |        0/6.00           0/6.00           0/6.00           2/6.00           3/6.00                           | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             33.3%            50.0%                            | 
|TERMINAL (d)       |        0/6 (0%)         0/6 (0%)         0/6 (0%)         2/6 (33%)        3/6 (50%)                        | 
|FIRST INCIDENCE    |        ---              ---              ---              3 (T)            3 (T)                            | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.004 **       (e)              (e)              P=0.229          P=0.101                          | 
|POLY 3             |        P<0.001 **       (e)              (e)              P=0.215          P=0.068                          | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P=0.215          P=0.068                          | 
|POLY 6             |        P<0.001 **       (e)              (e)              P=0.215          P=0.068                          | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.229          P=0.101                          | 
|COCH-ARM / FISHERS |        P=0.004 **       (e)              (e)              P=0.227          P=0.091                          | 
|ORDER RESTRICTED   |        P=0.007 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          50 MG/KG         150MG/KG         1500MG/K         2000MG/K                         | 
|                   |        48 HR            48 HR            48 HR            48 HR            48 HR                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver, Median Lobe: Centrilobular                                                                                                | 
|     Infiltration Cellular Mononuclear Cell                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/6 (0%)         0/6 (0%)         0/6 (0%)         6/6 (100%)       6/6 (100%)                       | 
|POLY-3 RATE (b)    |        0/6.00           0/6.00           0/6.00           6/6.00           6/6.00                           | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             100.0%           100.0%                           | 
|TERMINAL (d)       |        0/6 (0%)         0/6 (0%)         0/6 (0%)         6/6 (100%)       6/6 (100%)                       | 
|FIRST INCIDENCE    |        ---              ---              ---              3 (T)            3 (T)                            | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.003 **       P=0.003 **                       | 
|POLY 3             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 6             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.003 **       P=0.003 **                       | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  08/18/04                           EXPERIMENT: 55801 TEST: 06                                            Page 4       
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -           ACETAMINOPHEN (4-HYDROXYACETANILI            
                                         Terminal Sacrifice at 1 weeks                                                              
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          50 MG/KG         150MG/KG         1500MG/K         2000MG/K                         | 
|                   |        48 HR            48 HR            48 HR            48 HR            48 HR                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver, Median Lobe: Centrilobular                                                                                                | 
|     Necrosis                                                                                                                    | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/6 (0%)         0/6 (0%)         0/6 (0%)         6/6 (100%)       6/6 (100%)                       | 
|POLY-3 RATE (b)    |        0/6.00           0/6.00           0/6.00           6/6.00           6/6.00                           | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             100.0%           100.0%                           | 
|TERMINAL (d)       |        0/6 (0%)         0/6 (0%)         0/6 (0%)         6/6 (100%)       6/6 (100%)                       | 
|FIRST INCIDENCE    |        ---              ---              ---              3 (T)            3 (T)                            | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.003 **       P=0.003 **                       | 
|POLY 3             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 6             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.003 **       P=0.003 **                       | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          50 MG/KG         150MG/KG         1500MG/K         2000MG/K                         | 
|                   |        48 HR            48 HR            48 HR            48 HR            48 HR                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver, Median Lobe: Hepatocyte                                                                                                   | 
|     Degeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/6 (0%)         0/6 (0%)         0/6 (0%)         5/6 (83%)        3/6 (50%)                        | 
|POLY-3 RATE (b)    |        0/6.00           0/6.00           0/6.00           5/6.00           3/6.00                           | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             83.3%            50.0%                            | 
|TERMINAL (d)       |        0/6 (0%)         0/6 (0%)         0/6 (0%)         5/6 (83%)        3/6 (50%)                        | 
|FIRST INCIDENCE    |        ---              ---              ---              3 (T)            3 (T)                            | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.012 *        P=0.101                          | 
|POLY 3             |        P<0.001 **       (e)              (e)              P<0.001 **       P=0.068                          | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P<0.001 **       P=0.068                          | 
|POLY 6             |        P<0.001 **       (e)              (e)              P<0.001 **       P=0.068                          | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.012 *        P=0.101                          | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P=0.008 **       P=0.091                          | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  08/18/04                           EXPERIMENT: 55801 TEST: 06                                            Page 5       
Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -           ACETAMINOPHEN (4-HYDROXYACETANILI            
                                         Terminal Sacrifice at 1 weeks                                                              
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          50 MG/KG         150MG/KG         1500MG/K         2000MG/K                         | 
|                   |        48 HR            48 HR            48 HR            48 HR            48 HR                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver, Median Lobe: Hepatocyte                                                                                                   | 
|     Regeneration                                                                                                                | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/6 (0%)         0/6 (0%)         0/6 (0%)         5/6 (83%)        6/6 (100%)                       | 
|POLY-3 RATE (b)    |        0/6.00           0/6.00           0/6.00           5/6.00           6/6.00                           | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             83.3%            100.0%                           | 
|TERMINAL (d)       |        0/6 (0%)         0/6 (0%)         0/6 (0%)         5/6 (83%)        6/6 (100%)                       | 
|FIRST INCIDENCE    |        ---              ---              ---              3 (T)            3 (T)                            | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.012 *        P=0.003 **                       | 
|POLY 3             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|POLY 6             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **                       | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.012 *        P=0.003 **                       | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P=0.008 **       P<0.001 **                       | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)                              | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        0 MG/KG          50 MG/KG         150MG/KG         1500MG/K         2000MG/K                         | 
|                   |        48 HR            48 HR            48 HR            48 HR            48 HR                            | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver, Median Lobe: Sinusoid                                                                                                     | 
|     Congestion                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/6 (0%)         0/6 (0%)         0/6 (0%)         5/6 (83%)        3/6 (50%)                        | 
|POLY-3 RATE (b)    |        0/6.00           0/6.00           0/6.00           5/6.00           3/6.00                           | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             83.3%            50.0%                            | 
|TERMINAL (d)       |        0/6 (0%)         0/6 (0%)         0/6 (0%)         5/6 (83%)        3/6 (50%)                        | 
|FIRST INCIDENCE    |        ---              ---              ---              3 (T)            3 (T)                            | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.012 *        P=0.101                          | 
|POLY 3             |        P<0.001 **       (e)              (e)              P<0.001 **       P=0.068                          | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P<0.001 **       P=0.068                          | 
|POLY 6             |        P<0.001 **       (e)              (e)              P<0.001 **       P=0.068                          | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.012 *        P=0.101                          | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P=0.008 **       P=0.091                          | 
|ORDER RESTRICTED   |        P<0.001 **       (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).