National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/19296

TDMS Study 97006-01 Pathology Tables

                                                                                                                                   
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Northwest                                  METHYL ISOBUTYL KETONE                                DATE: 11/11/04       
EXPERIMENT: 97006 TEST: 01                                                                                     TIME: 10:08:51       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-05452                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C97006       
PATHOLOGIST: RENNE, ROGER                                                                                      CAS: 108-10-1        
Rats(F 344)                                                                                                                         
-----------------------------                                                                                                       
FOR ALL DOSES THE TUMOR RATES IN THE FOLLOWING TISSUES/ORGANS ARE                                                                   
BASED ON NUMBER OF TISSUES EXAMINED.  IN OTHER TISSUES/ORGANS RATES                                                                 
ARE BASED ON THE NUMBER OF ANIMALS NECROPSIED.                                                                                      
                                                 ---------------                                                                    
                                                 Kidney                                                                             
                                                 Kidney, Renal Tubule (Step Section)                                                
                                                 Kidney, Renal Tubule (Step and Original Sections)                                  
                                                                                                                                   
NTP                                        STATISTICAL ANALYSIS OF PRIMARY TUMORS                              REPORT: PEIRPT08     
LAB: Battelle Northwest                                  METHYL ISOBUTYL KETONE                                DATE: 11/11/04       
EXPERIMENT: 97006 TEST: 01                                                                                     TIME: 10:08:51       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                        
CONT: N01-ES-05452                              ROUTE: RESPIRATORY EXPOSURE WHOLE BODY                         NTP C#: C97006       
PATHOLOGIST: RENNE, ROGER                                                                                      CAS: 108-10-1        
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF                 METHYL ISOBUTYL KETONE                                                                           
===============================================================                                                                     
Male Rats                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Kidney, Renal Tubule (Step Section)    Adenoma                                                                                      
                                       Carcinoma and Adenoma                                                                        
                                       Hyperplasia                                                                                  
                                       Hyperplasia and Adenoma                                                                      
                                       Hyperplasia, Carcinoma or Adenoma                                                            
Kidney, Renal Tubule (Step and Original Sections)                                                                                   
                                       Adenoma                                                                                      
                                       Carcinoma and Adenoma                                                                        
                                       Hyperplasia                                                                                  
                                       Hyperplasia and Adenoma                                                                      
                                       Hyperplasia, Carcinoma or Adenoma                                                            
Kidney: Renal Tubule                   Adenoma                                                                                      
                                       Carcinoma or Adenoma                                                                         
                                       Hyperplasia                                                                                  
                                       Hyperplasia and Adenoma                                                                      
                                       Hyperplasia, Carcinoma or Adenoma                                                            
All Organs                             Leukemia: Lymphocytic, Monocytic, Mononuclear, or Undifferentiated                           
                                       Benign Tumors                                                                                
                                       Malignant Tumors                                                                             
                                       Malignant and Benign Tumors                                                                  
===============================================================                                                                     
Female Rats                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Kidney: Renal Tubule                   Mesenchymal Tumor Malignant                                                                  
===============================================================                                                                     
                                                                                                                                   
       Date:  11/11/04                           EXPERIMENT: 97006 TEST: 01                                            Page 1       
                     Statistical Analysis of Primary Tumors in Rats(F 344)        -                  METHYL ISOBUTYL KETONE         
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney, Renal Tubule (Step Section)                                                                                              | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    3/50 (6%)    1/50 (2%)    7/50 (14%)  |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/44.54      3/41.93      1/42.20      7/41.57     |0/44.82      0/44.54      0/41.95      0/43.18      | 
|POLY-3 PERCENT (g) |     4.5%         7.2%         2.4%         16.8%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/32 (3%)    2/28 (7%)    0/25 (0%)    5/19 (26%)  |0/35 (0%)    0/34 (0%)    0/26 (0%)    0/32 (0%)    | 
|FIRST INCIDENCE    |     713          677          695          677         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.006 **   P=0.433      P=0.564N     P=0.014 *   |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.029 *    P=0.473      P=0.519N     P=0.062     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.032 *    P=0.483      P=0.514N     P=0.071     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.024 *    P=0.461      P=0.527N     P=0.048 *   |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.015 *    P=0.454      P=0.529N     P=0.023 *   |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.036 *    P=0.500      P=0.500N     P=0.080     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.019 *    (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney, Renal Tubule (Step Section)                                                                                              | 
|     Carcinoma and Adenoma                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    3/50 (6%)    1/50 (2%)    7/50 (14%)  |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/44.54      3/41.93      1/42.20      7/41.57     |0/44.82      0/44.54      0/41.95      0/43.18      | 
|POLY-3 PERCENT (g) |     4.5%         7.2%         2.4%         16.8%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/32 (3%)    2/28 (7%)    0/25 (0%)    5/19 (26%)  |0/35 (0%)    0/34 (0%)    0/26 (0%)    0/32 (0%)    | 
|FIRST INCIDENCE    |     713          677          695          677         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.006 **   P=0.433      P=0.564N     P=0.014 *   |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.029 *    P=0.473      P=0.519N     P=0.062     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.032 *    P=0.483      P=0.514N     P=0.071     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.024 *    P=0.461      P=0.527N     P=0.048 *   |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.015 *    P=0.454      P=0.529N     P=0.023 *   |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.036 *    P=0.500      P=0.500N     P=0.080     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.019 *    (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/11/04                           EXPERIMENT: 97006 TEST: 01                                            Page 2       
                     Statistical Analysis of Primary Tumors in Rats(F 344)       -                  METHYL ISOBUTYL KETONE          
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney, Renal Tubule (Step Section)                                                                                              | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    3/50 (6%)    4/50 (8%)    6/50 (12%)  |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/44.48      3/42.57      4/42.35      6/42.38     |0/44.82      0/44.54      0/41.95      0/43.18      | 
|POLY-3 PERCENT (g) |     0.0%         7.1%         9.5%         14.2%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/32 (0%)    2/28 (7%)    2/25 (8%)    1/19 (5%)   |0/35 (0%)    0/34 (0%)    0/26 (0%)    0/32 (0%)    | 
|FIRST INCIDENCE    |     ---          405          667          645         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.004 **   P=0.106      P=0.042 *    P=0.007 **  |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.011 *    P=0.111      P=0.054      P=0.013 *   |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.013 *    P=0.114      P=0.055      P=0.014 *   |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.009 **   P=0.106      P=0.051      P=0.010 *   |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.015 *    P=0.153      P=0.054      P=0.018 *   |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.015 *    P=0.121      P=0.059      P=0.013 *   |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.007 **   (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney, Renal Tubule (Step Section)                                                                                              | 
|     Hyperplasia and Adenoma                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    6/50 (12%)   5/50 (10%)   13/50 (26%) |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/44.54      6/42.76      5/42.47      13/42.63    |0/44.82      0/44.54      0/41.95      0/43.18      | 
|POLY-3 PERCENT (g) |     4.5%         14.0%        11.8%        30.5%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/32 (3%)    4/28 (14%)   2/25 (8%)    6/19 (32%)  |0/35 (0%)    0/34 (0%)    0/26 (0%)    0/32 (0%)    | 
|FIRST INCIDENCE    |     713          405          667          645         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.102      P=0.151      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P<0.001 **   P=0.119      P=0.196      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P<0.001 **   P=0.125      P=0.201      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P<0.001 **   P=0.112      P=0.189      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.137      P=0.186      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.134      P=0.218      P=0.002 **  |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/11/04                           EXPERIMENT: 97006 TEST: 01                                            Page 3       
                     Statistical Analysis of Primary Tumors in Rats(F 344)       -                  METHYL ISOBUTYL KETONE          
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney, Renal Tubule (Step Section)                                                                                              | 
|     Hyperplasia, Carcinoma or Adenoma                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    6/50 (12%)   5/50 (10%)   13/50 (26%) |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/44.54      6/42.76      5/42.47      13/42.63    |0/44.82      0/44.54      0/41.95      0/43.18      | 
|POLY-3 PERCENT (g) |     4.5%         14.0%        11.8%        30.5%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/32 (3%)    4/28 (14%)   2/25 (8%)    6/19 (32%)  |0/35 (0%)    0/34 (0%)    0/26 (0%)    0/32 (0%)    | 
|FIRST INCIDENCE    |     713          405          667          645         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.102      P=0.151      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P<0.001 **   P=0.119      P=0.196      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P<0.001 **   P=0.125      P=0.201      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P<0.001 **   P=0.112      P=0.189      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.137      P=0.186      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.134      P=0.218      P=0.002 **  |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney, Renal Tubule (Step and Original Sections)                                                                                | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    3/50 (6%)    3/50 (6%)    10/50 (20%) |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/44.54      3/41.93      3/42.32      10/41.60    |0/44.82      0/44.54      0/41.95      0/43.18      | 
|POLY-3 PERCENT (g) |     4.5%         7.2%         7.1%         24.0%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/32 (3%)    2/28 (7%)    1/25 (4%)    7/19 (37%)  |0/35 (0%)    0/34 (0%)    0/26 (0%)    0/32 (0%)    | 
|FIRST INCIDENCE    |     713          677          695          677         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.433      P=0.420      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.002 **   P=0.473      P=0.477      P=0.009 **  |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.002 **   P=0.483      P=0.482      P=0.011 *   |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P<0.001 **   P=0.461      P=0.468      P=0.005 **  |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.454      P=0.463      P=0.002 **  |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.003 **   P=0.500      P=0.500      P=0.014 *   |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/11/04                           EXPERIMENT: 97006 TEST: 01                                            Page 4       
                     Statistical Analysis of Primary Tumors in Rats(F 344)       -                  METHYL ISOBUTYL KETONE          
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney, Renal Tubule (Step and Original Sections)                                                                                | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/44.48      1/41.74      0/42.07      2/41.33     |0/44.82      0/44.54      0/41.95      0/43.18      | 
|POLY-3 PERCENT (g) |     0.0%         2.4%         0.0%         4.8%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/32 (0%)    1/28 (4%)    0/25 (0%)    2/19 (11%)  |0/35 (0%)    0/34 (0%)    0/26 (0%)    0/32 (0%)    | 
|FIRST INCIDENCE    |     ---          726 (T)      ---          726 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.069      P=0.473      (e)          P=0.132     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.129      P=0.487      (e)          P=0.221     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.134      P=0.492      (e)          P=0.229     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.119      P=0.482      (e)          P=0.205     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          P=0.473      (e)          P=0.132     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.140      P=0.500      (e)          P=0.247     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.064      (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney, Renal Tubule (Step and Original Sections)                                                                                | 
|     Carcinoma and Adenoma                                                                                                       | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    4/50 (8%)    3/50 (6%)    11/50 (22%) |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/44.54      4/41.93      3/42.32      11/41.60    |0/44.82      0/44.54      0/41.95      0/43.18      | 
|POLY-3 PERCENT (g) |     4.5%         9.5%         7.1%         26.4%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/32 (3%)    3/28 (11%)   1/25 (4%)    8/19 (42%)  |0/35 (0%)    0/34 (0%)    0/26 (0%)    0/32 (0%)    | 
|FIRST INCIDENCE    |     713          677          695          677         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.275      P=0.420      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P<0.001 **   P=0.309      P=0.477      P=0.004 **  |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P<0.001 **   P=0.320      P=0.482      P=0.005 **  |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P<0.001 **   P=0.297      P=0.468      P=0.002 **  |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.286      P=0.463      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.002 **   P=0.339      P=0.500      P=0.007 **  |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/11/04                           EXPERIMENT: 97006 TEST: 01                                            Page 5       
                     Statistical Analysis of Primary Tumors in Rats(F 344)       -                  METHYL ISOBUTYL KETONE          
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney, Renal Tubule (Step and Original Sections)                                                                                | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    14/50 (28%)  7/50 (14%)   21/50 (42%) |1/50 (2%)    1/50 (2%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/44.48      14/43.08     7/42.45      21/43.68    |1/44.90      1/44.54      0/41.95      1/43.18      | 
|POLY-3 PERCENT (g) |     2.3%         32.5%        16.5%        48.1%       |2.2%         2.3%         0.0%         2.3%         | 
|TERMINAL (d)       |     1/32 (3%)    11/28 (39%)  4/25 (16%)   9/19 (47%)  |0/35 (0%)    1/34 (3%)    0/26 (0%)    1/32 (3%)    | 
|FIRST INCIDENCE    |     726 (T)      405          667          609         |707          727 (T)      ---          727 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P<0.001 **   P=0.017 *    P<0.001 **  |P=0.647N     P=0.760      P=0.559N     P=0.735      | 
|POLY 3             |     P<0.001 **   P<0.001 **   P=0.025 *    P<0.001 **  |P=0.623N     P=0.759      P=0.514N     P=0.752      | 
|POLY 1.5           |     P<0.001 **   P<0.001 **   P=0.026 *    P<0.001 **  |P=0.619N     P=0.759      P=0.507N     P=0.755      | 
|POLY 6             |     P<0.001 **   P<0.001 **   P=0.023 *    P<0.001 **  |P=0.629N     P=0.759      P=0.525N     P=0.750      | 
|LOGISTIC REGRESSION|     P<0.001 **   P<0.001 **   P=0.022 *    P<0.001 **  |P=0.633N     P=0.762      P=0.518N     P=0.753      | 
|COCH-ARM / FISHERS |     P<0.001 **   P<0.001 **   P=0.030 *    P<0.001 **  |P=0.616N     P=0.753N     P=0.500N     P=0.753N     | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P=0.550N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney, Renal Tubule (Step and Original Sections)                                                                                | 
|     Hyperplasia and Adenoma                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    17/50 (34%)  10/50 (20%)  25/50 (50%) |1/50 (2%)    1/50 (2%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     3/44.54      17/43.27     10/42.69     25/43.87    |1/44.90      1/44.54      0/41.95      1/43.18      | 
|POLY-3 PERCENT (g) |     6.7%         39.3%        23.4%        57.0%       |2.2%         2.3%         0.0%         2.3%         | 
|TERMINAL (d)       |     2/32 (6%)    13/28 (46%)  5/25 (20%)   12/19 (63%) |0/35 (0%)    1/34 (3%)    0/26 (0%)    1/32 (3%)    | 
|FIRST INCIDENCE    |     713          405          667          609         |707          727 (T)      ---          727 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P<0.001 **   P=0.018 *    P<0.001 **  |P=0.647N     P=0.760      P=0.559N     P=0.735      | 
|POLY 3             |     P<0.001 **   P<0.001 **   P=0.027 *    P<0.001 **  |P=0.623N     P=0.759      P=0.514N     P=0.752      | 
|POLY 1.5           |     P<0.001 **   P<0.001 **   P=0.029 *    P<0.001 **  |P=0.619N     P=0.759      P=0.507N     P=0.755      | 
|POLY 6             |     P<0.001 **   P<0.001 **   P=0.025 *    P<0.001 **  |P=0.629N     P=0.759      P=0.525N     P=0.750      | 
|LOGISTIC REGRESSION|     P<0.001 **   P<0.001 **   P=0.024 *    P<0.001 **  |P=0.633N     P=0.762      P=0.518N     P=0.753      | 
|COCH-ARM / FISHERS |     P<0.001 **   P<0.001 **   P=0.036 *    P<0.001 **  |P=0.616N     P=0.753N     P=0.500N     P=0.753N     | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P=0.550N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/11/04                           EXPERIMENT: 97006 TEST: 01                                            Page 6       
                     Statistical Analysis of Primary Tumors in Rats(F 344)       -                  METHYL ISOBUTYL KETONE          
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney, Renal Tubule (Step and Original Sections)                                                                                | 
|     Hyperplasia, Carcinoma or Adenoma                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     3/50 (6%)    17/50 (34%)  10/50 (20%)  26/50 (52%) |1/50 (2%)    1/50 (2%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     3/44.54      17/43.27     10/42.69     26/43.87    |1/44.90      1/44.54      0/41.95      1/43.18      | 
|POLY-3 PERCENT (g) |     6.7%         39.3%        23.4%        59.3%       |2.2%         2.3%         0.0%         2.3%         | 
|TERMINAL (d)       |     2/32 (6%)    13/28 (46%)  5/25 (20%)   13/19 (68%) |0/35 (0%)    1/34 (3%)    0/26 (0%)    1/32 (3%)    | 
|FIRST INCIDENCE    |     713          405          667          609         |707          727 (T)      ---          727 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P<0.001 **   P=0.018 *    P<0.001 **  |P=0.647N     P=0.760      P=0.559N     P=0.735      | 
|POLY 3             |     P<0.001 **   P<0.001 **   P=0.027 *    P<0.001 **  |P=0.623N     P=0.759      P=0.514N     P=0.752      | 
|POLY 1.5           |     P<0.001 **   P<0.001 **   P=0.029 *    P<0.001 **  |P=0.619N     P=0.759      P=0.507N     P=0.755      | 
|POLY 6             |     P<0.001 **   P<0.001 **   P=0.025 *    P<0.001 **  |P=0.629N     P=0.759      P=0.525N     P=0.750      | 
|LOGISTIC REGRESSION|     P<0.001 **   P<0.001 **   P=0.024 *    P<0.001 **  |P=0.633N     P=0.762      P=0.518N     P=0.753      | 
|COCH-ARM / FISHERS |     P<0.001 **   P<0.001 **   P=0.036 *    P<0.001 **  |P=0.616N     P=0.753N     P=0.500N     P=0.753N     | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P=0.550N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Adenoma                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    2/50 (4%)    3/50 (6%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/44.48      0/41.74      2/42.20      3/41.36     |0/44.82      0/44.54      0/41.95      0/43.18      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         4.7%         7.3%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/32 (0%)    0/28 (0%)    1/25 (4%)    2/19 (11%)  |0/35 (0%)    0/34 (0%)    0/26 (0%)    0/32 (0%)    | 
|FIRST INCIDENCE    |     ---          ---          695          719         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.008 **   (e)          P=0.204      P=0.049 *   |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.024 *    (e)          P=0.225      P=0.106     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.026 *    (e)          P=0.228      P=0.113     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.020 *    (e)          P=0.221      P=0.094     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.012 *    (e)          P=0.219      P=0.052     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.028 *    (e)          P=0.247      P=0.121     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.031 *    (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/11/04                           EXPERIMENT: 97006 TEST: 01                                            Page 7       
                     Statistical Analysis of Primary Tumors in Rats(F 344)       -                  METHYL ISOBUTYL KETONE          
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Carcinoma                                                                                                                   | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/44.48      1/41.74      0/42.07      2/41.33     |0/44.82      0/44.54      0/41.95      0/43.18      | 
|POLY-3 PERCENT (g) |     0.0%         2.4%         0.0%         4.8%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/32 (0%)    1/28 (4%)    0/25 (0%)    2/19 (11%)  |0/35 (0%)    0/34 (0%)    0/26 (0%)    0/32 (0%)    | 
|FIRST INCIDENCE    |     ---          726 (T)      ---          726 (T)     |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.069      P=0.473      (e)          P=0.132     |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.129      P=0.487      (e)          P=0.221     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.134      P=0.492      (e)          P=0.229     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.119      P=0.482      (e)          P=0.205     |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     (e)          P=0.473      (e)          P=0.132     |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.140      P=0.500      (e)          P=0.247     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.064      (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Carcinoma or Adenoma                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    2/50 (4%)    4/50 (8%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     0/44.48      1/41.74      2/42.20      4/41.36     |0/44.82      0/44.54      0/41.95      0/43.18      | 
|POLY-3 PERCENT (g) |     0.0%         2.4%         4.7%         9.7%        |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     0/32 (0%)    1/28 (4%)    1/25 (4%)    3/19 (16%)  |0/35 (0%)    0/34 (0%)    0/26 (0%)    0/32 (0%)    | 
|FIRST INCIDENCE    |     ---          726 (T)      695          719         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.004 **   P=0.473      P=0.204      P=0.018 *   |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.018 *    P=0.487      P=0.225      P=0.051     |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.020 *    P=0.492      P=0.228      P=0.056     |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P=0.014 *    P=0.482      P=0.221      P=0.043 *   |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P=0.007 **   P=0.473      P=0.219      P=0.018 *   |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.022 *    P=0.500      P=0.247      P=0.059     |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P=0.015 *    (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/11/04                           EXPERIMENT: 97006 TEST: 01                                            Page 8       
                     Statistical Analysis of Primary Tumors in Rats(F 344)       -                  METHYL ISOBUTYL KETONE          
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Hyperplasia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    11/50 (22%)  3/50 (6%)    18/50 (36%) |1/50 (2%)    1/50 (2%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/44.48      11/42.25     3/42.17      18/42.93    |1/44.90      1/44.54      0/41.95      1/43.18      | 
|POLY-3 PERCENT (g) |     2.3%         26.0%        7.1%         41.9%       |2.2%         2.3%         0.0%         2.3%         | 
|TERMINAL (d)       |     1/32 (3%)    9/28 (32%)   2/25 (8%)    9/19 (47%)  |0/35 (0%)    1/34 (3%)    0/26 (0%)    1/32 (3%)    | 
|FIRST INCIDENCE    |     726 (T)      658          702          609         |707          727 (T)      ---          727 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P<0.001 **   P=0.231      P<0.001 **  |P=0.647N     P=0.760      P=0.559N     P=0.735      | 
|POLY 3             |     P<0.001 **   P<0.001 **   P=0.286      P<0.001 **  |P=0.623N     P=0.759      P=0.514N     P=0.752      | 
|POLY 1.5           |     P<0.001 **   P<0.001 **   P=0.291      P<0.001 **  |P=0.619N     P=0.759      P=0.507N     P=0.755      | 
|POLY 6             |     P<0.001 **   P<0.001 **   P=0.278      P<0.001 **  |P=0.629N     P=0.759      P=0.525N     P=0.750      | 
|LOGISTIC REGRESSION|     P<0.001 **   P<0.001 **   P=0.255      P<0.001 **  |P=0.633N     P=0.762      P=0.518N     P=0.753      | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.002 **   P=0.309      P<0.001 **  |P=0.616N     P=0.753N     P=0.500N     P=0.753N     | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P=0.550N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Hyperplasia and Adenoma                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    11/50 (22%)  5/50 (10%)   19/50 (38%) |1/50 (2%)    1/50 (2%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/44.48      11/42.25     5/42.29      19/42.93    |1/44.90      1/44.54      0/41.95      1/43.18      | 
|POLY-3 PERCENT (g) |     2.3%         26.0%        11.8%        44.3%       |2.2%         2.3%         0.0%         2.3%         | 
|TERMINAL (d)       |     1/32 (3%)    9/28 (32%)   3/25 (12%)   10/19 (53%) |0/35 (0%)    1/34 (3%)    0/26 (0%)    1/32 (3%)    | 
|FIRST INCIDENCE    |     726 (T)      658          695          609         |707          727 (T)      ---          727 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P<0.001 **   P=0.066      P<0.001 **  |P=0.647N     P=0.760      P=0.559N     P=0.735      | 
|POLY 3             |     P<0.001 **   P<0.001 **   P=0.089      P<0.001 **  |P=0.623N     P=0.759      P=0.514N     P=0.752      | 
|POLY 1.5           |     P<0.001 **   P<0.001 **   P=0.092      P<0.001 **  |P=0.619N     P=0.759      P=0.507N     P=0.755      | 
|POLY 6             |     P<0.001 **   P<0.001 **   P=0.085      P<0.001 **  |P=0.629N     P=0.759      P=0.525N     P=0.750      | 
|LOGISTIC REGRESSION|     P<0.001 **   P<0.001 **   P=0.078      P<0.001 **  |P=0.633N     P=0.762      P=0.518N     P=0.753      | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.002 **   P=0.102      P<0.001 **  |P=0.616N     P=0.753N     P=0.500N     P=0.753N     | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P=0.550N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/11/04                           EXPERIMENT: 97006 TEST: 01                                            Page 9       
                     Statistical Analysis of Primary Tumors in Rats(F 344)       -                  METHYL ISOBUTYL KETONE          
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Hyperplasia, Carcinoma or Adenoma                                                                                           | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     1/50 (2%)    11/50 (22%)  5/50 (10%)   20/50 (40%) |1/50 (2%)    1/50 (2%)    0/50 (0%)    1/50 (2%)    | 
|POLY-3 RATE (b)    |     1/44.48      11/42.25     5/42.29      20/42.93    |1/44.90      1/44.54      0/41.95      1/43.18      | 
|POLY-3 PERCENT (g) |     2.3%         26.0%        11.8%        46.6%       |2.2%         2.3%         0.0%         2.3%         | 
|TERMINAL (d)       |     1/32 (3%)    9/28 (32%)   3/25 (12%)   11/19 (58%) |0/35 (0%)    1/34 (3%)    0/26 (0%)    1/32 (3%)    | 
|FIRST INCIDENCE    |     726 (T)      658          695          609         |707          727 (T)      ---          727 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P<0.001 **   P=0.066      P<0.001 **  |P=0.647N     P=0.760      P=0.559N     P=0.735      | 
|POLY 3             |     P<0.001 **   P<0.001 **   P=0.089      P<0.001 **  |P=0.623N     P=0.759      P=0.514N     P=0.752      | 
|POLY 1.5           |     P<0.001 **   P<0.001 **   P=0.092      P<0.001 **  |P=0.619N     P=0.759      P=0.507N     P=0.755      | 
|POLY 6             |     P<0.001 **   P<0.001 **   P=0.085      P<0.001 **  |P=0.629N     P=0.759      P=0.525N     P=0.750      | 
|LOGISTIC REGRESSION|     P<0.001 **   P<0.001 **   P=0.078      P<0.001 **  |P=0.633N     P=0.762      P=0.518N     P=0.753      | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.002 **   P=0.102      P<0.001 **  |P=0.616N     P=0.753N     P=0.500N     P=0.753N     | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P=0.550N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney: Renal Tubule                                                                                                             | 
|     Mesenchymal Tumor Malignant                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |                                                        |                                                    | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     0/44.48      0/41.74      0/42.07      0/41.33     |0/44.82      0/44.54      0/41.95      2/43.18      | 
|POLY-3 PERCENT (g) |     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         4.6%         | 
|TERMINAL (d)       |     0/32 (0%)    0/28 (0%)    0/25 (0%)    0/19 (0%)   |0/35 (0%)    0/34 (0%)    0/26 (0%)    2/32 (6%)    | 
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          ---          727 (T)      | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.044 *    (e)          (e)          P=0.219      | 
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.043 *    (e)          (e)          P=0.229      | 
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.044 *    (e)          (e)          P=0.232      | 
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.043 *    (e)          (e)          P=0.227      | 
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          P=0.219      | 
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.046 *    (e)          (e)          P=0.247      | 
|ORDER RESTRICTED   |     (e)          (e)          (e)          (e)         |P=0.027 *    (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/11/04                           EXPERIMENT: 97006 TEST: 01                                            Page 10      
                     Statistical Analysis of Primary Tumors in Rats(F 344)       -                  METHYL ISOBUTYL KETONE          
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Leukemia: Lymphocytic, Monocytic, Mononuclear, or                                                                           | 
|     Undifferentiated                                                                                                            | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     6/50 (12%)   5/50 (10%)   11/50 (22%)  15/50 (30%) |3/50 (6%)    4/50 (8%)    3/50 (6%)    2/50 (4%)    | 
|POLY-3 RATE (b)    |     6/46.29      5/42.63      11/45.20     15/44.60    |3/45.69      4/45.76      3/42.75      2/43.77      | 
|POLY-3 PERCENT (g) |     13.0%        11.7%        24.3%        33.6%       |6.6%         8.7%         7.0%         4.6%         | 
|TERMINAL (d)       |     1/32 (3%)    2/28 (7%)    1/25 (4%)    2/19 (11%)  |0/35 (0%)    0/34 (0%)    0/26 (0%)    0/32 (0%)    | 
|FIRST INCIDENCE    |     468          602          539          567         |583          537          637          548          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P=0.002 **   P=0.577N     P=0.124      P=0.010 *   |P=0.386N     P=0.497      P=0.576      P=0.529N     | 
|POLY 3             |     P=0.003 **   P=0.558N     P=0.128      P=0.016 *   |P=0.370N     P=0.501      P=0.631      P=0.520N     | 
|POLY 1.5           |     P=0.004 **   P=0.536N     P=0.128      P=0.019 *   |P=0.360N     P=0.500      P=0.647      P=0.513N     | 
|POLY 6             |     P=0.002 **   P=0.583N     P=0.127      P=0.012 *   |P=0.383N     P=0.502      P=0.606      P=0.527N     | 
|LOGISTIC REGRESSION|     P=0.005 **   P=0.432N     P=0.196      P=0.035 *   |P=0.293N     P=0.515      P=0.642N     P=0.459N     | 
|COCH-ARM / FISHERS |     P=0.004 **   P=0.500N     P=0.143      P=0.024 *   |P=0.344N     P=0.500      P=0.661N     P=0.500N     | 
|ORDER RESTRICTED   |     P=0.006 **   (e)          (e)          (e)         |P=0.445N     (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Benign Tumors                                                                                                               | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     2/50 (4%)    3/50 (6%)    3/50 (6%)    10/50 (20%) |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    | 
|POLY-3 RATE (b)    |     2/44.54      3/41.93      3/42.32      10/41.60    |0/44.82      0/44.54      0/41.95      0/43.18      | 
|POLY-3 PERCENT (g) |     4.5%         7.2%         7.1%         24.0%       |0.0%         0.0%         0.0%         0.0%         | 
|TERMINAL (d)       |     1/32 (3%)    2/28 (7%)    1/25 (4%)    7/19 (37%)  |0/35 (0%)    0/34 (0%)    0/26 (0%)    0/32 (0%)    | 
|FIRST INCIDENCE    |     713          677          695          677         |---          ---          ---          ---          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.433      P=0.420      P<0.001 **  |(e)          (e)          (e)          (e)          | 
|POLY 3             |     P=0.002 **   P=0.473      P=0.477      P=0.009 **  |(e)          (e)          (e)          (e)          | 
|POLY 1.5           |     P=0.002 **   P=0.483      P=0.482      P=0.011 *   |(e)          (e)          (e)          (e)          | 
|POLY 6             |     P<0.001 **   P=0.461      P=0.468      P=0.005 **  |(e)          (e)          (e)          (e)          | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.454      P=0.463      P=0.002 **  |(e)          (e)          (e)          (e)          | 
|COCH-ARM / FISHERS |     P=0.003 **   P=0.500      P=0.500      P=0.014 *   |(e)          (e)          (e)          (e)          | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |(e)          (e)          (e)          (e)          | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  11/11/04                           EXPERIMENT: 97006 TEST: 01                                            Page 11      
                     Statistical Analysis of Primary Tumors in Rats(F 344)       -                  METHYL ISOBUTYL KETONE          
                                         Terminal Sacrifice at 104 weeks                                                            
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant Tumors                                                                                                            | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     9/50 (18%)   20/50 (40%)  19/50 (38%)  34/50 (68%) |3/50 (6%)    5/50 (10%)   4/50 (8%)    5/50 (10%)   | 
|POLY-3 RATE (b)    |     9/46.35      20/44.16     19/45.64     34/46.49    |3/45.69      5/45.76      4/43.41      5/43.77      | 
|POLY-3 PERCENT (g) |     19.4%        45.3%        41.6%        73.1%       |6.6%         10.9%        9.2%         11.4%        | 
|TERMINAL (d)       |     3/32 (9%)    13/28 (46%)  6/25 (24%)   13/19 (68%) |0/35 (0%)    1/34 (3%)    0/26 (0%)    3/32 (9%)    | 
|FIRST INCIDENCE    |     468          405          539          567         |583          537          509          548          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.009 **   P=0.017 *    P<0.001 **  |P=0.308      P=0.357      P=0.421      P=0.322      | 
|POLY 3             |     P<0.001 **   P=0.006 **   P=0.016 *    P<0.001 **  |P=0.319      P=0.357      P=0.472      P=0.333      | 
|POLY 1.5           |     P<0.001 **   P=0.008 **   P=0.016 *    P<0.001 **  |P=0.331      P=0.357      P=0.487      P=0.341      | 
|POLY 6             |     P<0.001 **   P=0.005 **   P=0.016 *    P<0.001 **  |P=0.305      P=0.358      P=0.447      P=0.324      | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.014 *    P=0.026 *    P<0.001 **  |P=0.393      P=0.366      P=0.529      P=0.370      | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.013 *    P=0.022 *    P<0.001 **  |P=0.350      P=0.357      P=0.500      P=0.357      | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P=0.346      (e)          (e)          (e)          | 
|=================================================================================================================================| 
|                   |                                                        |                                                    | 
|                   |                              Males                     |                       Females                      | 
|Dose               |     CONTROL      450 PPM      900 PPM      1800 PPM    |CONTROL      450 PPM      900 PPM      1800 PPM     | 
|                   |                                                        |                                                    | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|All Organs                                                                                                                       | 
|     Malignant and Benign Tumors                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|TUMOR RATES        |     #            #            #            #           |#            #            #            #            | 
|-----------        |                                                        |                                                    | 
|OVERALL (a)        |     9/50 (18%)   20/50 (40%)  19/50 (38%)  34/50 (68%) |3/50 (6%)    5/50 (10%)   4/50 (8%)    5/50 (10%)   | 
|POLY-3 RATE (b)    |     9/46.35      20/44.16     19/45.64     34/46.49    |3/45.69      5/45.76      4/43.41      5/43.77      | 
|POLY-3 PERCENT (g) |     19.4%        45.3%        41.6%        73.1%       |6.6%         10.9%        9.2%         11.4%        | 
|TERMINAL (d)       |     3/32 (9%)    13/28 (46%)  6/25 (24%)   13/19 (68%) |0/35 (0%)    1/34 (3%)    0/26 (0%)    3/32 (9%)    | 
|FIRST INCIDENCE    |     468          405          539          567         |583          537          509          548          | 
|-------------------|                                                        |                                                    | 
|STATISTICAL TESTS  |                                                        |                                                    | 
|-------------------|                                                        |                                                    | 
|LIFE TABLE         |     P<0.001 **   P=0.009 **   P=0.017 *    P<0.001 **  |P=0.308      P=0.357      P=0.421      P=0.322      | 
|POLY 3             |     P<0.001 **   P=0.006 **   P=0.016 *    P<0.001 **  |P=0.319      P=0.357      P=0.472      P=0.333      | 
|POLY 1.5           |     P<0.001 **   P=0.008 **   P=0.016 *    P<0.001 **  |P=0.331      P=0.357      P=0.487      P=0.341      | 
|POLY 6             |     P<0.001 **   P=0.005 **   P=0.016 *    P<0.001 **  |P=0.305      P=0.358      P=0.447      P=0.324      | 
|LOGISTIC REGRESSION|     P<0.001 **   P=0.014 *    P=0.026 *    P<0.001 **  |P=0.393      P=0.366      P=0.529      P=0.370      | 
|COCH-ARM / FISHERS |     P<0.001 **   P=0.013 *    P=0.022 *    P<0.001 **  |P=0.350      P=0.357      P=0.500      P=0.357      | 
|ORDER RESTRICTED   |     P<0.001 **   (e)          (e)          (e)         |P=0.346      (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.