National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/16653

TDMS Study 61938-01 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Northwest                                      1-NITROPYRENE                                     DATE: 10/18/04       
EXPERIMENT: 61938 TEST: 01                                                                                     TIME: 08:36:31       
TEST TYPE:  SUBCHRON 90-DAY                                                                                    PAGE:       1        
CONT: N01-ES-85232                              ROUTE: RESPIRATORY EXPOSURE NASAL                              NTP C#: C61938       
PATHOLOGIST: R. MILLER                       R. RENNE                        P.                                CAS: 5522-43-0       
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               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
                                                                                                                                   
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Northwest                                      1-NITROPYRENE                                     DATE: 10/18/04       
EXPERIMENT: 61938 TEST: 01                                                                                     TIME: 08:36:31       
TEST TYPE:  SUBCHRON 90-DAY                                                                                                         
CONT: N01-ES-85232                              ROUTE: RESPIRATORY EXPOSURE NASAL                              NTP C#: C61938       
PATHOLOGIST: R. MILLER                       R. RENNE                        P.                                CAS: 5522-43-0       
                                                                                                                                    
                                                                                                                                    
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS                                                                               
IN THE ANALYSIS OF                     1-NITROPYRENE                                                                                
===============================================================                                                                     
Male Rats                                                                                                                           
------------                                                                                                                        
Organ                                 Morphology                                                                                    
-----                                 ----------                                                                                    
Larynx: Epiglottis                     Metaplasia                                                                                   
Liver                                  Hepatodiaphragmatic Nodule                                                                   
Lung: Bronchus                         Metaplasia                                                                                   
Nose: Respiratory Epithelium           Cytoplasmic Alteration                                                                       
===============================================================                                                                     
Female Rats                                                                                                                         
------------                                                                                                                        
Organ                                  Morphology                                                                                   
-----                                  ----------                                                                                   
Larynx: Epiglottis                     Metaplasia                                                                                   
Liver                                  Hepatodiaphragmatic Nodule                                                                   
Lung                                   Hemorrhage                                                                                   
                                       Inflammation Chronic                                                                         
Lung: Bronchus                         Metaplasia                                                                                   
Nose: Respiratory Epithelium           Cytoplasmic Alteration                                                                       
===============================================================                                                                     
                                                                                                                                   
       Date:  10/18/04                           EXPERIMENT: 61938 TEST: 01                                            Page 1       
Statistical Analysis of Non-neoplastic Lesions in        Rats(FISCHER 344)  -                      1-NITROPYRENE                    
                                         Terminal Sacrifice at 13 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Epididymis                                                                                                                       | 
|     Hypospermia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        9/9 (100%)       10/10 (100%)     10/10 (100%)     9/9 (100%)       10/10 (100%)     10/10 (100%)    | 
|POLY-3 RATE (b)    |        9/9.00           10/10.00         10/10.00         9/9.00           10/10.00         10/10.00        | 
|POLY-3 PERCENT (g) |        100.0%           100.0%           100.0%           100.0%           100.0%           100.0%          | 
|TERMINAL (d)       |        9/9 (100%)       10/10 (100%)     10/10 (100%)     9/9 (100%)       10/10 (100%)     10/10 (100%)    | 
|FIRST INCIDENCE    |        91 (T)           91 (T)           91 (T)           91 (T)           91 (T)           91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Epididymis                                                                                                                       | 
|     Hypospermia                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                                                                                                             | 
|POLY-3 RATE (b)    |                                                                                                             | 
|POLY-3 PERCENT (g) |                                                                                                             | 
|TERMINAL (d)       |                                                                                                             | 
|FIRST INCIDENCE    |                                                                                                             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                                                                                                             | 
|POLY 3             |                                                                                                             | 
|POLY 1.5           |                                                                                                             | 
|POLY 6             |                                                                                                             | 
|LOGISTIC REGRESSION|                                                                                                             | 
|COCH-ARM / FISHERS |                                                                                                             | 
|ORDER RESTRICTED   |                                                                                                             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/18/04                           EXPERIMENT: 61938 TEST: 01                                            Page 2       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      1-NITROPYRENE
                                         Terminal Sacrifice at 13 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart                                                                                                                            | 
|     Cardiomyopathy                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        6/10 (60%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         4/10 (40%)      | 
|POLY-3 RATE (b)    |        6/10.00          0/0.00           0/0.00           0/0.00           0/0.00           4/10.00         | 
|POLY-3 PERCENT (g) |        60.0%            0.0%             0.0%             0.0%             0.0%             40.0%           | 
|TERMINAL (d)       |        6/10 (60%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         4/10 (40%)      | 
|FIRST INCIDENCE    |        91 (T)           ---              ---              ---              ---              91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.271N         P=1.000          P=1.000          P=1.000          P=1.000N         P=0.331N        | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              P=0.333N        | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              P=0.333N        | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              P=0.333N        | 
|LOGISTIC REGRESSION|        P=0.271N         (e)              (e)              (e)              (e)              P=0.331N        | 
|COCH-ARM / FISHERS |        P=0.266N         P=1.000          P=1.000          P=1.000          P=1.000          P=0.328N        | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Heart                                                                                                                            | 
|     Cardiomyopathy                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        4/10 (40%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         4/10 (40%)      | 
|POLY-3 RATE (b)    |        4/10.00          0/0.00           0/0.00           0/0.00           0/0.00           4/10.00         | 
|POLY-3 PERCENT (g) |        40.0%            0.0%             0.0%             0.0%             0.0%             40.0%           | 
|TERMINAL (d)       |        4/10 (40%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         4/10 (40%)      | 
|FIRST INCIDENCE    |        91 (T)           ---              ---              ---              ---              91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.605          P=1.000          P=1.000          P=1.000          P=1.000          P=0.672         | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              P=0.667         | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              P=0.667         | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              P=0.667         | 
|LOGISTIC REGRESSION|        P=0.605          (e)              (e)              (e)              (e)              P=0.672         | 
|COCH-ARM / FISHERS |        P=0.608          P=1.000          P=1.000          P=1.000          P=1.000          P=0.675N        | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/18/04                           EXPERIMENT: 61938 TEST: 01                                            Page 3       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      1-NITROPYRENE
                                         Terminal Sacrifice at 13 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        5/10 (50%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         5/10 (50%)      | 
|POLY-3 RATE (b)    |        5/10.00          0/0.00           0/0.00           0/0.00           0/0.00           5/10.00         | 
|POLY-3 PERCENT (g) |        50.0%            0.0%             0.0%             0.0%             0.0%             50.0%           | 
|TERMINAL (d)       |        5/10 (50%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         5/10 (50%)      | 
|FIRST INCIDENCE    |        91 (T)           ---              ---              ---              ---              91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.603          P=1.000N         P=1.000N         P=1.000N         P=1.000N         P=0.669         | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              P=0.664         | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              P=0.664         | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              P=0.664         | 
|LOGISTIC REGRESSION|        P=0.603          (e)              (e)              (e)              (e)              P=0.669         | 
|COCH-ARM / FISHERS |        P=0.606          P=1.000          P=1.000          P=1.000          P=1.000          P=0.672N        | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Kidney                                                                                                                           | 
|     Nephropathy                                                                                                                 | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/10 (10%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         1/10 (10%)      | 
|POLY-3 RATE (b)    |        1/10.00          0/0.00           0/0.00           0/0.00           0/0.00           1/10.00         | 
|POLY-3 PERCENT (g) |        10.0%            0.0%             0.0%             0.0%             0.0%             10.0%           | 
|TERMINAL (d)       |        1/10 (10%)       0/0 (0%)         0/0 (0%)         0/0 (0%)         0/0 (0%)         1/10 (10%)      | 
|FIRST INCIDENCE    |        91 (T)           ---              ---              ---              ---              91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.669          P=1.000N         P=1.000N         P=1.000N         P=1.000N         P=0.766         | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              P=0.760         | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              P=0.760         | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              P=0.760         | 
|LOGISTIC REGRESSION|        P=0.669          (e)              (e)              (e)              (e)              P=0.766         | 
|COCH-ARM / FISHERS |        P=0.673          P=1.000          P=1.000          P=1.000          P=1.000          P=0.763N        | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/18/04                           EXPERIMENT: 61938 TEST: 01                                            Page 4       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      1-NITROPYRENE
                                         Terminal Sacrifice at 13 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Larynx: Epiglottis                                                                                                               | 
|     Metaplasia                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/10 (0%)        0/10 (0%)        5/10 (50%)       10/10 (100%)     10/10 (100%)     10/10 (100%)    | 
|POLY-3 RATE (b)    |        0/10.00          0/10.00          5/10.00          10/10.00         10/10.00         10/10.00        | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             50.0%            100.0%           100.0%           100.0%          | 
|TERMINAL (d)       |        0/10 (0%)        0/10 (0%)        5/10 (50%)       10/10 (100%)     10/10 (100%)     10/10 (100%)    | 
|FIRST INCIDENCE    |        ---              ---              91 (T)           91 (T)           91 (T)           91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              P=0.022 *        P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 3             |        P<0.001 **       (e)              P=0.008 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       (e)              P=0.008 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 6             |        P<0.001 **       (e)              P=0.008 **       P<0.001 **       P<0.001 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        (e)              (e)              P=0.022 *        P<0.001 **       P<0.001 **       P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              P=0.016 *        P<0.001 **       P<0.001 **       P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Larynx: Epiglottis                                                                                                               | 
|     Metaplasia                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/10 (0%)        4/10 (40%)       4/10 (40%)       10/10 (100%)     10/10 (100%)     10/10 (100%)    | 
|POLY-3 RATE (b)    |        0/10.00          4/10.00          4/10.00          10/10.00         10/10.00         10/10.00        | 
|POLY-3 PERCENT (g) |        0.0%             40.0%            40.0%            100.0%           100.0%           100.0%          | 
|TERMINAL (d)       |        0/10 (0%)        4/10 (40%)       4/10 (40%)       10/10 (100%)     10/10 (100%)     10/10 (100%)    | 
|FIRST INCIDENCE    |        ---              91 (T)           91 (T)           91 (T)           91 (T)           91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       P=0.051          P=0.051          P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 3             |        P<0.001 **       P=0.033 *        P=0.033 *        P<0.001 **       P<0.001 **       P<0.001N**      | 
|POLY 1.5           |        P<0.001 **       P=0.033 *        P=0.033 *        P<0.001 **       P<0.001 **       P<0.001N**      | 
|POLY 6             |        P<0.001 **       P=0.033 *        P=0.033 *        P<0.001 **       P<0.001 **       P<0.001N**      | 
|LOGISTIC REGRESSION|        (e)              P=0.051          P=0.051          P<0.001 **       P<0.001 **       P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       P=0.043 *        P=0.043 *        P<0.001 **       P<0.001 **       P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/18/04                           EXPERIMENT: 61938 TEST: 01                                            Page 5       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      1-NITROPYRENE
                                         Terminal Sacrifice at 13 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatodiaphragmatic Nodule                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        2/10 (20%)       2/2 (100%)       4/4 (100%)       1/1 (100%)       1/1 (100%)       1/10 (10%)      | 
|POLY-3 RATE (b)    |        2/10.00          2/2.00           4/4.00           1/1.00           1/1.00           1/10.00         | 
|POLY-3 PERCENT (g) |        20.0%            100.0%           100.0%           100.0%           100.0%           10.0%           | 
|TERMINAL (d)       |        2/10 (20%)       2/2 (100%)       4/4 (100%)       1/1 (100%)       1/1 (100%)       1/10 (10%)      | 
|FIRST INCIDENCE    |        91 (T)           91 (T)           91 (T)           91 (T)           91 (T)           91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.038N*        P=0.095          P=0.020 *        P=0.305          P=0.305          P=0.500N        | 
|POLY 3             |        P=0.004N**       P=0.053          P=0.002 **       P=0.286          P=0.286          P=0.500N        | 
|POLY 1.5           |        P=0.004N**       P=0.053          P=0.002 **       P=0.286          P=0.286          P=0.500N        | 
|POLY 6             |        P=0.004N**       P=0.053          P=0.002 **       P=0.286          P=0.286          P=0.500N        | 
|LOGISTIC REGRESSION|        P=0.038N*        P=0.095          P=0.020 *        P=0.305          P=0.305          P=0.500N        | 
|COCH-ARM / FISHERS |        P=0.035N*        P=0.091          P=0.015 *        P=0.273          P=0.273          P=0.500N        | 
|ORDER RESTRICTED   |        P<0.001N**       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Liver                                                                                                                            | 
|     Hepatodiaphragmatic Nodule                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/10 (0%)        2/3 (67%)        1/1 (100%)       4/4 (100%)       1/1 (100%)       1/10 (10%)      | 
|POLY-3 RATE (b)    |        0/10.00          2/3.00           1/1.00           4/4.00           1/1.00           1/10.00         | 
|POLY-3 PERCENT (g) |        0.0%             66.7%            100.0%           100.0%           100.0%           10.0%           | 
|TERMINAL (d)       |        0/10 (0%)        2/3 (67%)        1/1 (100%)       4/4 (100%)       1/1 (100%)       1/10 (10%)      | 
|FIRST INCIDENCE    |        ---              91 (T)           91 (T)           91 (T)           91 (T)           91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.182N         P=0.034 *        P=0.077          P<0.001 **       P=0.077          P=0.500         | 
|POLY 3             |        P=0.051N         P=0.003 **       P=0.091          P<0.001 **       P=0.091          P=0.500         | 
|POLY 1.5           |        P=0.051N         P=0.003 **       P=0.091          P<0.001 **       P=0.091          P=0.500         | 
|POLY 6             |        P=0.051N         P=0.003 **       P=0.091          P<0.001 **       P=0.091          P=0.500         | 
|LOGISTIC REGRESSION|        (e)              P=0.034 *        P=0.077          P<0.001 **       P=0.077          P=0.500         | 
|COCH-ARM / FISHERS |        P=0.178N         P=0.038 *        P=0.091          P<0.001 **       P=0.091          P=0.500         | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/18/04                           EXPERIMENT: 61938 TEST: 01                                            Page 6       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      1-NITROPYRENE
                                         Terminal Sacrifice at 13 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        10/10 (100%)     8/8 (100%)       10/10 (100%)     9/10 (90%)       10/10 (100%)     10/10 (100%)    | 
|POLY-3 RATE (b)    |        10/10.00         8/8.00           10/10.00         9/10.00          10/10.00         10/10.00        | 
|POLY-3 PERCENT (g) |        100.0%           100.0%           100.0%           90.0%            100.0%           100.0%          | 
|TERMINAL (d)       |        10/10 (100%)     8/8 (100%)       10/10 (100%)     9/10 (90%)       10/10 (100%)     10/10 (100%)    | 
|FIRST INCIDENCE    |        91 (T)           91 (T)           91 (T)           91 (T)           91 (T)           91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.695          (e)              (e)              P=0.500N         (e)              (e)             | 
|POLY 3             |        P=0.695          (e)              (e)              P=0.500N         (e)              (e)             | 
|POLY 1.5           |        P=0.695          (e)              (e)              P=0.500N         (e)              (e)             | 
|POLY 6             |        P=0.695          (e)              (e)              P=0.500N         (e)              (e)             | 
|LOGISTIC REGRESSION|        P=0.695          (e)              (e)              P=0.500N         (e)              (e)             | 
|COCH-ARM / FISHERS |        P=0.697          (e)              (e)              P=0.500N         (e)              (e)             | 
|ORDER RESTRICTED   |        P=0.513N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Hemorrhage                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        10/10 (100%)     8/10 (80%)       6/10 (60%)       9/10 (90%)       7/10 (70%)       9/10 (90%)      | 
|POLY-3 RATE (b)    |        10/10.00         8/10.00          6/10.00          9/10.00          7/10.00          9/10.00         | 
|POLY-3 PERCENT (g) |        100.0%           80.0%            60.0%            90.0%            70.0%            90.0%           | 
|TERMINAL (d)       |        10/10 (100%)     8/10 (80%)       6/10 (60%)       9/10 (90%)       7/10 (70%)       9/10 (90%)      | 
|FIRST INCIDENCE    |        91 (T)           91 (T)           91 (T)           91 (T)           91 (T)           91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.459          P=0.234N         P=0.051N         P=0.500N         P=0.111N         P=0.500N        | 
|POLY 3             |        P=0.458          P=0.227N         P=0.033N*        P=0.500N         P=0.095N         P=0.500N        | 
|POLY 1.5           |        P=0.458          P=0.227N         P=0.033N*        P=0.500N         P=0.095N         P=0.500N        | 
|POLY 6             |        P=0.458          P=0.227N         P=0.033N*        P=0.500N         P=0.095N         P=0.500N        | 
|LOGISTIC REGRESSION|        P=0.459          P=0.234N         P=0.051N         P=0.500N         P=0.111N         P=0.500N        | 
|COCH-ARM / FISHERS |        P=0.458          P=0.237N         P=0.043N*        P=0.500N         P=0.105N         P=0.500N        | 
|ORDER RESTRICTED   |        P=0.159N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/18/04                           EXPERIMENT: 61938 TEST: 01                                            Page 7       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      1-NITROPYRENE
                                         Terminal Sacrifice at 13 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/10 (0%)        3/8 (38%)        1/10 (10%)       2/10 (20%)       1/10 (10%)       0/10 (0%)       | 
|POLY-3 RATE (b)    |        0/10.00          3/8.00           1/10.00          2/10.00          1/10.00          0/10.00         | 
|POLY-3 PERCENT (g) |        0.0%             37.5%            10.0%            20.0%            10.0%            0.0%            | 
|TERMINAL (d)       |        0/10 (0%)        3/8 (38%)        1/10 (10%)       2/10 (20%)       1/10 (10%)       0/10 (0%)       | 
|FIRST INCIDENCE    |        ---              91 (T)           91 (T)           91 (T)           91 (T)           ---             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.171N         P=0.074          P=0.500          P=0.234          P=0.500          (e)             | 
|POLY 3             |        P=0.163N         P=0.053          P=0.500          P=0.227          P=0.500          (e)             | 
|POLY 1.5           |        P=0.163N         P=0.053          P=0.500          P=0.227          P=0.500          (e)             | 
|POLY 6             |        P=0.163N         P=0.053          P=0.500          P=0.227          P=0.500          (e)             | 
|LOGISTIC REGRESSION|        (e)              P=0.074          P=0.500          P=0.234          P=0.500          (e)             | 
|COCH-ARM / FISHERS |        P=0.169N         P=0.069          P=0.500          P=0.237          P=0.500          (e)             | 
|ORDER RESTRICTED   |        P=0.205N         (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung                                                                                                                             | 
|     Inflammation Chronic                                                                                                        | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/10 (0%)        5/10 (50%)       2/10 (20%)       0/10 (0%)        2/10 (20%)       2/10 (20%)      | 
|POLY-3 RATE (b)    |        0/10.00          5/10.00          2/10.00          0/10.00          2/10.00          2/10.00         | 
|POLY-3 PERCENT (g) |        0.0%             50.0%            20.0%            0.0%             20.0%            20.0%           | 
|TERMINAL (d)       |        0/10 (0%)        5/10 (50%)       2/10 (20%)       0/10 (0%)        2/10 (20%)       2/10 (20%)      | 
|FIRST INCIDENCE    |        ---              91 (T)           91 (T)           ---              91 (T)           91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.602N         P=0.022 *        P=0.234          (e)              P=0.234          P=0.234         | 
|POLY 3             |        P=0.609N         P=0.008 **       P=0.227          (e)              P=0.227          P=0.227         | 
|POLY 1.5           |        P=0.609N         P=0.008 **       P=0.227          (e)              P=0.227          P=0.227         | 
|POLY 6             |        P=0.609N         P=0.008 **       P=0.227          (e)              P=0.227          P=0.227         | 
|LOGISTIC REGRESSION|        (e)              P=0.022 *        P=0.234          (e)              P=0.234          P=0.234         | 
|COCH-ARM / FISHERS |        P=0.603N         P=0.016 *        P=0.237          (e)              P=0.237          P=0.237         | 
|ORDER RESTRICTED   |        P=0.152          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/18/04                           EXPERIMENT: 61938 TEST: 01                                            Page 8       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      1-NITROPYRENE
                                         Terminal Sacrifice at 13 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Bronchus                                                                                                                   | 
|     Metaplasia                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/10 (0%)        0/8 (0%)         0/10 (0%)        1/10 (10%)       2/10 (20%)       5/10 (50%)      | 
|POLY-3 RATE (b)    |        0/10.00          0/8.00           0/10.00          1/10.00          2/10.00          5/10.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             10.0%            20.0%            50.0%           | 
|TERMINAL (d)       |        0/10 (0%)        0/8 (0%)         0/10 (0%)        1/10 (10%)       2/10 (20%)       5/10 (50%)      | 
|FIRST INCIDENCE    |        ---              ---              ---              91 (T)           91 (T)           91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.500          P=0.234          P=0.022 *       | 
|POLY 3             |        P<0.001 **       (e)              (e)              P=0.500          P=0.227          P=0.008 **      | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P=0.500          P=0.227          P=0.008 **      | 
|POLY 6             |        P<0.001 **       (e)              (e)              P=0.500          P=0.227          P=0.008 **      | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.500          P=0.234          P=0.022 *       | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P=0.500          P=0.237          P=0.016 *       | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Lung: Bronchus                                                                                                                   | 
|     Metaplasia                                                                                                                  | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        2/10 (20%)       3/10 (30%)      | 
|POLY-3 RATE (b)    |        0/10.00          0/10.00          0/10.00          0/10.00          2/10.00          3/10.00         | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             0.0%             20.0%            30.0%           | 
|TERMINAL (d)       |        0/10 (0%)        0/10 (0%)        0/10 (0%)        0/10 (0%)        2/10 (20%)       3/10 (30%)      | 
|FIRST INCIDENCE    |        ---              ---              ---              ---              91 (T)           91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.002 **       (e)              (e)              (e)              P=0.234          P=0.111         | 
|POLY 3             |        P<0.001 **       (e)              (e)              (e)              P=0.227          P=0.095         | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              (e)              P=0.227          P=0.095         | 
|POLY 6             |        P<0.001 **       (e)              (e)              (e)              P=0.227          P=0.095         | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              P=0.234          P=0.111         | 
|COCH-ARM / FISHERS |        P=0.002 **       (e)              (e)              (e)              P=0.237          P=0.105         | 
|ORDER RESTRICTED   |        P=0.007 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/18/04                           EXPERIMENT: 61938 TEST: 01                                            Page 9       
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      1-NITROPYRENE
                                         Terminal Sacrifice at 13 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose: Olfactory Epithelium                                                                                                       | 
|     Cytoplasmic Alteration                                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)    | 
|POLY-3 RATE (b)    |        10/10.00         10/10.00         10/10.00         10/10.00         10/10.00         10/10.00        | 
|POLY-3 PERCENT (g) |        100.0%           100.0%           100.0%           100.0%           100.0%           100.0%          | 
|TERMINAL (d)       |        10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)    | 
|FIRST INCIDENCE    |        91 (T)           91 (T)           91 (T)           91 (T)           91 (T)           91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose: Olfactory Epithelium                                                                                                       | 
|     Cytoplasmic Alteration                                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)    | 
|POLY-3 RATE (b)    |        10/10.00         10/10.00         10/10.00         10/10.00         10/10.00         10/10.00        | 
|POLY-3 PERCENT (g) |        100.0%           100.0%           100.0%           100.0%           100.0%           100.0%          | 
|TERMINAL (d)       |        10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)    | 
|FIRST INCIDENCE    |        91 (T)           91 (T)           91 (T)           91 (T)           91 (T)           91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/18/04                           EXPERIMENT: 61938 TEST: 01                                            Page 10      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      1-NITROPYRENE
                                         Terminal Sacrifice at 13 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose: Respiratory Epithelium                                                                                                     | 
|     Cytoplasmic Alteration                                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/10 (0%)        0/10 (0%)        0/10 (0%)        8/10 (80%)       10/10 (100%)     10/10 (100%)    | 
|POLY-3 RATE (b)    |        0/10.00          0/10.00          0/10.00          8/10.00          10/10.00         10/10.00        | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             80.0%            100.0%           100.0%          | 
|TERMINAL (d)       |        0/10 (0%)        0/10 (0%)        0/10 (0%)        8/10 (80%)       10/10 (100%)     10/10 (100%)    | 
|FIRST INCIDENCE    |        ---              ---              ---              91 (T)           91 (T)           91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 3             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **       P<0.001 **      | 
|POLY 6             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **       P<0.001 **      | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P<0.001 **       P<0.001 **       P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **       P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Nose: Respiratory Epithelium                                                                                                     | 
|     Cytoplasmic Alteration                                                                                                      | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        0/10 (0%)        0/10 (0%)        0/10 (0%)        6/10 (60%)       10/10 (100%)     10/10 (100%)    | 
|POLY-3 RATE (b)    |        0/10.00          0/10.00          0/10.00          6/10.00          10/10.00         10/10.00        | 
|POLY-3 PERCENT (g) |        0.0%             0.0%             0.0%             60.0%            100.0%           100.0%          | 
|TERMINAL (d)       |        0/10 (0%)        0/10 (0%)        0/10 (0%)        6/10 (60%)       10/10 (100%)     10/10 (100%)    | 
|FIRST INCIDENCE    |        ---              ---              ---              91 (T)           91 (T)           91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P<0.001 **       (e)              (e)              P=0.009 **       P<0.001 **       P<0.001 **      | 
|POLY 3             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **       P<0.001N**      | 
|POLY 1.5           |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **       P<0.001N**      | 
|POLY 6             |        P<0.001 **       (e)              (e)              P<0.001 **       P<0.001 **       P<0.001N**      | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              P=0.009 **       P<0.001 **       P<0.001 **      | 
|COCH-ARM / FISHERS |        P<0.001 **       (e)              (e)              P=0.005 **       P<0.001 **       P<0.001 **      | 
|ORDER RESTRICTED   |        P<0.001 **       (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/18/04                           EXPERIMENT: 61938 TEST: 01                                            Page 11      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      1-NITROPYRENE
                                         Terminal Sacrifice at 13 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)    | 
|POLY-3 RATE (b)    |        10/10.00         10/10.00         10/10.00         10/10.00         10/10.00         10/10.00        | 
|POLY-3 PERCENT (g) |        100.0%           100.0%           100.0%           100.0%           100.0%           100.0%          | 
|TERMINAL (d)       |        10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)     10/10 (100%)    | 
|FIRST INCIDENCE    |        91 (T)           91 (T)           91 (T)           91 (T)           91 (T)           91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 3             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 1.5           |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|POLY 6             |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|LOGISTIC REGRESSION|        (e)              (e)              (e)              (e)              (e)              (e)             | 
|COCH-ARM / FISHERS |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|ORDER RESTRICTED   |        (e)              (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes                                                                                                                           | 
|     Atrophy                                                                                                                     | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                                                                                                             | 
|POLY-3 RATE (b)    |                                                                                                             | 
|POLY-3 PERCENT (g) |                                                                                                             | 
|TERMINAL (d)       |                                                                                                             | 
|FIRST INCIDENCE    |                                                                                                             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                                                                                                             | 
|POLY 3             |                                                                                                             | 
|POLY 1.5           |                                                                                                             | 
|POLY 6             |                                                                                                             | 
|LOGISTIC REGRESSION|                                                                                                             | 
|COCH-ARM / FISHERS |                                                                                                             | 
|ORDER RESTRICTED   |                                                                                                             | 
|=================================================================================================================================| 
                                                                                                                                   
       Date:  10/18/04                           EXPERIMENT: 61938 TEST: 01                                            Page 12      
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                      1-NITROPYRENE
                                         Terminal Sacrifice at 13 weeks                                                             
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Males                                                  | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes                                                                                                                           | 
|     Mineralization                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |        1/10 (10%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        2/10 (20%)       1/10 (10%)      | 
|POLY-3 RATE (b)    |        1/10.00          0/10.00          0/10.00          0/10.00          2/10.00          1/10.00         | 
|POLY-3 PERCENT (g) |        10.0%            0.0%             0.0%             0.0%             20.0%            10.0%           | 
|TERMINAL (d)       |        1/10 (10%)       0/10 (0%)        0/10 (0%)        0/10 (0%)        2/10 (20%)       1/10 (10%)      | 
|FIRST INCIDENCE    |        91 (T)           ---              ---              ---              91 (T)           91 (T)          | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |        P=0.269          P=0.500N         P=0.500N         P=0.500N         P=0.500          P=0.766         | 
|POLY 3             |        P=0.268          P=0.500N         P=0.500N         P=0.500N         P=0.500          P=0.760         | 
|POLY 1.5           |        P=0.268          P=0.500N         P=0.500N         P=0.500N         P=0.500          P=0.760         | 
|POLY 6             |        P=0.268          P=0.500N         P=0.500N         P=0.500N         P=0.500          P=0.760         | 
|LOGISTIC REGRESSION|        P=0.269          (e)              (e)              (e)              P=0.500          P=0.766         | 
|COCH-ARM / FISHERS |        P=0.267          P=0.500N         P=0.500N         P=0.500N         P=0.500          P=0.763N        | 
|ORDER RESTRICTED   |        P=0.232          (e)              (e)              (e)              (e)              (e)             | 
|=================================================================================================================================| 
|                   |                                                                                                             | 
|                   |                                                      Females                                                | 
|Dose               |        CONTROL          0.5              2.0              8.0              20.0             50.0            | 
|                   |                         MG/M3            MG/M3            MG/M3            MG/M3            MG/M3           | 
|=================================================================================================================================| 
|                                                                                                                                 | 
|Testes                                                                                                                           | 
|     Mineralization                                                                                                              | 
|                                                                                                                                 | 
|                                                                                                                                 | 
|---------------------------------------------------------------------------------------------------------------------------------| 
|LESION RATES       |                                                                                                             | 
|-----------        |                                                                                                             | 
|OVERALL (a)        |                                                                                                             | 
|POLY-3 RATE (b)    |                                                                                                             | 
|POLY-3 PERCENT (g) |                                                                                                             | 
|TERMINAL (d)       |                                                                                                             | 
|FIRST INCIDENCE    |                                                                                                             | 
|-------------------|                                                                                                             | 
|STATISTICAL TESTS  |                                                                                                             | 
|-------------------|                                                                                                             | 
|LIFE TABLE         |                                                                                                             | 
|POLY 3             |                                                                                                             | 
|POLY 1.5           |                                                                                                             | 
|POLY 6             |                                                                                                             | 
|LOGISTIC REGRESSION|                                                                                                             | 
|COCH-ARM / FISHERS |                                                                                                             | 
|ORDER RESTRICTED   |                                                                                                             | 
|=================================================================================================================================| 
(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.