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TDMS Study 88050-05 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                                     METHACRYLONITRILE                                   DATE: 02/24/00       
EXPERIMENT: 88050 TEST: 05                                                                                     TIME: 14:26:16       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-55388                              ROUTE: GAVAGE                                                  NTP C#: 88050B       
PATHOLOGIST: YARRINGTON, JOHN                                                                                  CAS: 126-98-7        
------------------------------------------------------------------------------------------------------------------------------------
                                                                                                                                    
                                                    FINAL#1 2 YEAR CHRONIC RATS                                                     
                                                                                                                                    

               REASONS FOR REMOVAL:    ALL                                                                                          
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
                                                                                                                                    
               REMOVAL DATE RANGE:     ALL                                                                                          
                                                                                                                                    
               TREATMENT GROUPS:       INCLUDE ALL                                                                                  
NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10   
LAB: Battelle Columbus                                     METHACRYLONITRILE                                   DATE: 02/24/00     
EXPERIMENT: 88050 TEST: 05                                                                                     TIME: 14:26:16     
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                      
CONT: NO1-ES-55388                              ROUTE: GAVAGE                                                  NTP C#: 88050B     
PATHOLOGIST: YARRINGTON, JOHN                                                                                  CAS: 126-98-7      



SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
IN THE ANALYSIS OF                METHACRYLONITRILE
===============================================================

Male Rats
------------
Organ                                 Morphology
-----                                 ----------
Adrenal Cortex                         Hematopoietic Cell Proliferation
                                       Vacuolization Cytoplasmic
Adrenal Medulla                        Hyperplasia
Heart                                  Cardiomyopathy
Kidney                                 Inflammation Chronic
                                       Nephropathy
Liver                                  Basophilic Focus
                                       Clear Cell Focus
                                       Fatty Change
                                       Inflammation Chronic
                                       Mixed Cell Focus
                                       Necrosis
                                       Vacuolization Cytoplasmic
Liver: Bile Duct                       Hyperplasia
Mammary Gland                          Galactocele
Mesentery: Fat                         Inflammation Chronic
Nose: Olfactory Epithelium             Atrophy
                                       Metaplasia
Pancreas                               Hyperplasia
Preputial Gland                        Inflammation Chronic
Prostate                               Hyperplasia
                                       Inflammation
Stomach, Glandular                     Ulcer
Thyroid Gland: C-Cell                  Hyperplasia
===============================================================
Female Rats
------------
Organ                                  Morphology
-----                                  ----------
Adrenal Cortex                         Angiectasis
                                       Necrosis
Bone Marrow                            Hyperplasia
Clitoral Gland                         Hyperplasia
Kidney                                 Inflammation Chronic
Liver                                  Fatty Change
                                       Mixed Cell Focus
                                       Vacuolization Cytoplasmic
Liver: Bile Duct                       Hyperplasia
Nose: Olfactory Epithelium             Atrophy
                                       Metaplasia
Spleen                                 Hematopoietic Cell Proliferation
Stomach, Glandular                     Erosion
Thyroid Gland: C-Cell                  Hyperplasia
===============================================================
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 1
                     Statistical Analysis of Non-neoplastic Lesions in        Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Angiectasis                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     5/50 (10%)   3/50 (6%)    12/50 (24%)  9/50 (18%)  |23/50 (46%)  6/50 (12%)   12/50 (24%)  19/50 (38%)  |
|POLY-3 ADJUSTED (b)|     12.2%        6.7%         26.5%        20.9%       |48.5%        13.6%        27.5%        42.6%        |
|TERMINAL (d)       |     5/25 (20%)   3/34 (9%)    10/35 (29%)  9/31 (29%)  |22/38 (58%)  5/33 (15%)   10/34 (29%)  18/36 (50%)  |
|FIRST INCIDENCE    |     729 (T)      729 (T)      480          729 (T)     |438          527          603          589          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.107      P=0.198N     P=0.174      P=0.322     |P=0.237      P<0.001N**   P=0.038N*    P=0.341N     |
|POLY 3             |     P=0.086      P=0.304N     P=0.080      P=0.219     |P=0.214      P<0.001N**   P=0.029N*    P=0.360N     |
|POLY 1.5           |     P=0.089      P=0.322N     P=0.068      P=0.211     |P=0.219      P<0.001N**   P=0.025N*    P=0.331N     |
|POLY 6             |     P=0.086      P=0.280N     P=0.102      P=0.234     |P=0.212      P<0.001N**   P=0.031N*    P=0.384N     |
|LOGISTIC REGRESSION|     P=0.094      P=0.198N     P=0.083      P=0.322     |P=0.205      P<0.001N**   P=0.033N*    P=0.369N     |
|COCH-ARM / FISHERS |     P=0.092      P=0.357N     P=0.054      P=0.194     |P=0.242      P<0.001N**   P=0.018N*    P=0.272N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Hematopoietic Cell Proliferation                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         4.6%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/25 (0%)    0/34 (0%)    0/35 (0%)    1/31 (3%)   |0/38 (0%)    0/33 (0%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          603         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.043 *    (e)          (e)          P=0.271     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.041 *    (e)          (e)          P=0.251     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.041 *    (e)          (e)          P=0.246     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.041 *    (e)          (e)          P=0.259     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.041 *    (e)          (e)          P=0.233     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.042 *    (e)          (e)          P=0.247     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 2
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     9/50 (18%)   10/50 (20%)  11/50 (22%)  8/50 (16%)  |7/50 (14%)   6/50 (12%)   10/50 (20%)  7/50 (14%)   |
|POLY-3 ADJUSTED (b)|     22.0%        22.2%        23.8%        18.5%       |15.0%        13.6%        23.1%        15.8%        |
|TERMINAL (d)       |     9/25 (36%)   10/34 (29%)  8/35 (23%)   7/31 (23%)  |7/38 (18%)   3/33 (9%)    7/34 (21%)   6/36 (17%)   |
|FIRST INCIDENCE    |     729 (T)      729 (T)      464          708         |731 (T)      690          690          641          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.318N     P=0.401N     P=0.509N     P=0.306N    |P=0.526      P=0.605N     P=0.218      P=0.570      |
|POLY 3             |     P=0.376N     P=0.595      P=0.524      P=0.451N    |P=0.505      P=0.545N     P=0.239      P=0.576      |
|POLY 1.5           |     P=0.378N     P=0.562      P=0.474      P=0.467N    |P=0.513      P=0.529N     P=0.256      P=0.587      |
|POLY 6             |     P=0.368N     P=0.569N     P=0.593      P=0.423N    |P=0.501      P=0.560N     P=0.229      P=0.566      |
|LOGISTIC REGRESSION|     P=0.374N     P=0.401N     P=0.450      P=0.339N    |P=0.498      P=0.580N     P=0.211      P=0.553      |
|COCH-ARM / FISHERS |     P=0.388N     P=0.500      P=0.402      P=0.500N    |P=0.530      P=0.500N     P=0.298      P=0.613N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         2.2%         0.0%        |0.0%         0.0%         0.0%         4.5%         |
|TERMINAL (d)       |     0/25 (0%)    0/34 (0%)    0/35 (0%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    0/34 (0%)    1/36 (3%)    |
|FIRST INCIDENCE    |     ---          ---          687          ---         |---          ---          ---          595          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.792N     (e)          P=0.548      (e)         |P=0.042 *    (e)          (e)          P=0.224      |
|POLY 3             |     P=0.785N     (e)          P=0.517      (e)         |P=0.040 *    (e)          (e)          P=0.227      |
|POLY 1.5           |     P=0.785N     (e)          P=0.510      (e)         |P=0.040 *    (e)          (e)          P=0.230      |
|POLY 6             |     P=0.784N     (e)          P=0.528      (e)         |P=0.040 *    (e)          (e)          P=0.225      |
|LOGISTIC REGRESSION|     P=0.786N     (e)          P=0.504      (e)         |P=0.043 *    (e)          (e)          P=0.261      |
|COCH-ARM / FISHERS |     P=0.786N     (e)          P=0.500      (e)         |P=0.042 *    (e)          (e)          P=0.247      |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 3
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Vacuolization Cytoplasmic                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     8/50 (16%)   3/50 (6%)    3/50 (6%)    5/50 (10%)  |4/50 (8%)    1/50 (2%)    2/50 (4%)    6/50 (12%)   |
|POLY-3 ADJUSTED (b)|     19.3%        6.6%         6.7%         11.1%       |8.4%         2.3%         4.6%         13.3%        |
|TERMINAL (d)       |     5/25 (20%)   2/34 (6%)    1/35 (3%)    1/31 (3%)   |2/38 (5%)    1/33 (3%)    1/34 (3%)    4/36 (11%)   |
|FIRST INCIDENCE    |     617          697          712          456         |514          731 (T)      696          553          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.423N     P=0.045N*    P=0.042N*    P=0.203N    |P=0.098      P=0.220N     P=0.391N     P=0.335      |
|POLY 3             |     P=0.448N     P=0.073N     P=0.077N     P=0.223N    |P=0.095      P=0.207N     P=0.385N     P=0.336      |
|POLY 1.5           |     P=0.450N     P=0.081N     P=0.085N     P=0.241N    |P=0.095      P=0.196N     P=0.369N     P=0.347      |
|POLY 6             |     P=0.446N     P=0.064N     P=0.065N     P=0.203N    |P=0.097      P=0.220N     P=0.398N     P=0.326      |
|LOGISTIC REGRESSION|     P=0.458N     P=0.067N     P=0.069N     P=0.288N    |P=0.100      P=0.135N     P=0.286N     P=0.443      |
|COCH-ARM / FISHERS |     P=0.457N     P=0.100N     P=0.100N     P=0.277N    |P=0.096      P=0.181N     P=0.339N     P=0.370      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Medulla                                                                                                                  |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     11/50 (22%)  5/50 (10%)   7/50 (14%)   7/50 (14%)  |2/50 (4%)    0/50 (0%)    3/50 (6%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     26.1%        11.0%        15.6%        16.0%       |4.3%         0.0%         7.0%         2.3%         |
|TERMINAL (d)       |     6/25 (24%)   4/34 (12%)   3/35 (9%)    6/31 (19%)  |2/38 (5%)    0/33 (0%)    1/34 (3%)    1/36 (3%)    |
|FIRST INCIDENCE    |     474          645          688          466         |731 (T)      ---          696          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.341N     P=0.031N*    P=0.091N     P=0.124N    |P=0.575N     P=0.270N     P=0.451      P=0.519N     |
|POLY 3             |     P=0.391N     P=0.058N     P=0.172N     P=0.186N    |P=0.582N     P=0.252N     P=0.465      P=0.519N     |
|POLY 1.5           |     P=0.386N     P=0.067N     P=0.190N     P=0.195N    |P=0.581N     P=0.247N     P=0.475      P=0.513N     |
|POLY 6             |     P=0.398N     P=0.049N*    P=0.146N     P=0.174N    |P=0.583N     P=0.259N     P=0.458      P=0.526N     |
|LOGISTIC REGRESSION|     P=0.377N     P=0.063N     P=0.173N     P=0.195N    |P=0.591N     (e)          P=0.455      P=0.519N     |
|COCH-ARM / FISHERS |     P=0.383N     P=0.086N     P=0.218N     P=0.218N    |P=0.577N     P=0.247N     P=0.500      P=0.500N     |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 4
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone Marrow                                                                                                                      |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     17/50 (34%)  14/50 (28%)  19/50 (38%)  20/50 (40%) |12/50 (24%)  11/50 (22%)  12/50 (24%)  25/50 (50%)  |
|POLY-3 ADJUSTED (b)|     38.7%        30.7%        41.7%        44.4%       |25.0%        24.3%        27.4%        52.2%        |
|TERMINAL (d)       |     10/25 (40%)  11/34 (32%)  16/35 (46%)  15/31 (48%) |8/38 (21%)   7/33 (21%)   10/34 (29%)  18/36 (50%)  |
|FIRST INCIDENCE    |     439          641          464          466         |438          441          434          246          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.255      P=0.110N     P=0.350N     P=0.573N    |P<0.001 **   P=0.556      P=0.471      P=0.007 **   |
|POLY 3             |     P=0.189      P=0.281N     P=0.472      P=0.372     |P<0.001 **   P=0.565N     P=0.491      P=0.004 **   |
|POLY 1.5           |     P=0.190      P=0.295N     P=0.451      P=0.364     |P<0.001 **   P=0.540N     P=0.524      P=0.005 **   |
|POLY 6             |     P=0.194      P=0.260N     P=0.515      P=0.394     |P<0.001 **   P=0.592N     P=0.460      P=0.004 **   |
|LOGISTIC REGRESSION|     P=0.194      P=0.279N     P=0.466      P=0.368     |P<0.001 **   P=0.442N     P=0.581      P=0.011 *    |
|COCH-ARM / FISHERS |     P=0.189      P=0.333N     P=0.418      P=0.339     |P<0.001 **   P=0.500N     P=0.592N     P=0.006 **   |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Brain                                                                                                                            |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    1/50 (2%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     4.8%         0.0%         2.2%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/25 (0%)    0/34 (0%)    0/35 (0%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     439          ---          691          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.266N     P=0.220N     P=0.454N     P=0.223N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.283N     P=0.220N     P=0.477N     P=0.230N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.279N     P=0.226N     P=0.487N     P=0.232N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.289N     P=0.213N     P=0.461N     P=0.226N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.290N     P=0.304N     P=0.545N     P=0.278N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.271N     P=0.247N     P=0.500N     P=0.247N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 5
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral Gland                                                                                                                   |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |1/49 (2%)    4/48 (8%)    5/50 (10%)   1/48 (2%)    |
|POLY-3 ADJUSTED (b)|                                                        |2.2%         9.5%         11.5%        2.4%         |
|TERMINAL (d)       |                                                        |1/37 (3%)    3/31 (10%)   2/34 (6%)    1/34 (3%)    |
|FIRST INCIDENCE    |                                                        |731 (T)      599          686          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.350N     P=0.138      P=0.087      P=0.743      |
|POLY 3             |                                                        |P=0.369N     P=0.155      P=0.090      P=0.742      |
|POLY 1.5           |                                                        |P=0.359N     P=0.161      P=0.094      P=0.747      |
|POLY 6             |                                                        |P=0.380N     P=0.148      P=0.087      P=0.738      |
|LOGISTIC REGRESSION|                                                        |P=0.352N     P=0.164      P=0.090      P=0.743      |
|COCH-ARM / FISHERS |                                                        |P=0.339N     P=0.175      P=0.107      P=0.747      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral Gland                                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |10/49 (20%)  7/48 (15%)   10/50 (20%)  2/48 (4%)    |
|POLY-3 ADJUSTED (b)|                                                        |21.9%        16.7%        23.3%        4.8%         |
|TERMINAL (d)       |                                                        |10/37 (27%)  4/31 (13%)   10/34 (29%)  2/34 (6%)    |
|FIRST INCIDENCE    |                                                        |731 (T)      686          731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.020N*    P=0.438N     P=0.516      P=0.021N*    |
|POLY 3             |                                                        |P=0.021N*    P=0.365N     P=0.541      P=0.019N*    |
|POLY 1.5           |                                                        |P=0.020N*    P=0.346N     P=0.564      P=0.018N*    |
|POLY 6             |                                                        |P=0.022N*    P=0.385N     P=0.523      P=0.021N*    |
|LOGISTIC REGRESSION|                                                        |P=0.022N*    P=0.421N     P=0.516      P=0.021N*    |
|COCH-ARM / FISHERS |                                                        |P=0.020N*    P=0.314N     P=0.579N     P=0.015N*    |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 6
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral Gland                                                                                                                   |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |6/49 (12%)   2/48 (4%)    5/50 (10%)   8/48 (17%)   |
|POLY-3 ADJUSTED (b)|                                                        |13.1%        4.8%         11.6%        18.7%        |
|TERMINAL (d)       |                                                        |5/37 (14%)   2/31 (7%)    4/34 (12%)   7/34 (21%)   |
|FIRST INCIDENCE    |                                                        |719          731 (T)      704          499          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.113      P=0.196N     P=0.564N     P=0.328      |
|POLY 3             |                                                        |P=0.107      P=0.164N     P=0.541N     P=0.336      |
|POLY 1.5           |                                                        |P=0.108      P=0.155N     P=0.524N     P=0.347      |
|POLY 6             |                                                        |P=0.108      P=0.176N     P=0.553N     P=0.324      |
|LOGISTIC REGRESSION|                                                        |P=0.098      P=0.193N     P=0.564N     P=0.333      |
|COCH-ARM / FISHERS |                                                        |P=0.111      P=0.141N     P=0.486N     P=0.371      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Esophagus: Periesophageal Tissue                                                                                                 |
|     Hemorrhage                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    1/50 (2%)    2/50 (4%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |0.0%         2.2%         4.5%         0.0%         |
|TERMINAL (d)       |     0/25 (0%)    0/34 (0%)    0/35 (0%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          328          508          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.524N     P=0.500      P=0.221      (e)          |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.534N     P=0.491      P=0.225      (e)          |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.528N     P=0.495      P=0.228      (e)          |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.539N     P=0.486      P=0.224      (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.386N     (e)          P=0.392      (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.515N     P=0.500      P=0.247      (e)          |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 7
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Eye                                                                                                                              |
|     Cataract                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/1 (0%)     1/1 (100%)   0/0 (0%)     0/0 (0%)    |4/4 (100%)   1/1 (100%)   3/3 (100%)   1/1 (100%)   |
|POLY-3 ADJUSTED (b)|     0.0%         100.0%       0.0%         0.0%        |100.0%       100.0%       100.0%       100.0%       |
|TERMINAL (d)       |     0/0 (0%)     1/1 (100%)   0/0 (0%)     0/0 (0%)    |3/3 (100%)   1/1 (100%)   2/2 (100%)   1/1 (100%)   |
|FIRST INCIDENCE    |     ---          729 (T)      ---          ---         |718          731 (T)      711          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=1.000N     P=1.000N     (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     (e)          P=1.000N     (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     (e)          P=1.000N     (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     (e)          P=1.000N     (e)          (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          P=1.000N     (e)          (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=1.000      P=0.500      (e)          (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Eye: Lens                                                                                                                        |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/1 (0%)     1/1 (100%)   0/0 (0%)     0/0 (0%)    |3/4 (75%)    0/1 (0%)     2/3 (67%)    0/1 (0%)     |
|POLY-3 ADJUSTED (b)|     0.0%         100.0%       0.0%         0.0%        |76.0%        0.0%         66.7%        0.0%         |
|TERMINAL (d)       |     0/0 (0%)     1/1 (100%)   0/0 (0%)     0/0 (0%)    |3/3 (100%)   0/1 (0%)     1/2 (50%)    0/1 (0%)     |
|FIRST INCIDENCE    |     ---          729 (T)      ---          ---         |731 (T)      ---          711          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=1.000N     P=1.000N     (e)          (e)         |P=0.278N     P=0.282N     P=0.732N     P=0.282N     |
|POLY 3             |     (e)          P=1.000N     (e)          (e)         |P=0.361N     P=0.403N     P=0.691N     P=0.403N     |
|POLY 1.5           |     (e)          P=1.000N     (e)          (e)         |P=0.364N     P=0.407N     P=0.694N     P=0.407N     |
|POLY 6             |     (e)          P=1.000N     (e)          (e)         |P=0.356N     P=0.394N     P=0.686N     P=0.394N     |
|LOGISTIC REGRESSION|     (e)          P=1.000N     (e)          (e)         |P=0.361N     (e)          P=0.765N     (e)          |
|COCH-ARM / FISHERS |     P=1.000      P=0.500      (e)          (e)         |P=0.358N     P=0.400N     P=0.714N     P=0.400N     |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 8
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Eye: Retina                                                                                                                      |
|     Degeneration                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/1 (0%)     0/1 (0%)     0/0 (0%)     0/0 (0%)    |3/4 (75%)    1/1 (100%)   3/3 (100%)   1/1 (100%)   |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |76.0%        100.0%       100.0%       100.0%       |
|TERMINAL (d)       |     0/0 (0%)     0/1 (0%)     0/0 (0%)     0/0 (0%)    |3/3 (100%)   1/1 (100%)   2/2 (100%)   1/1 (100%)   |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |731 (T)      731 (T)      711          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.789N     P=1.000      P=0.474      P=1.000      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.630      P=0.764      P=0.574      P=0.764      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.620      P=0.757      P=0.565      P=0.757      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.650      P=0.780      P=0.594      P=0.780      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.693      P=1.000      P=0.409      P=1.000      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.635      P=0.800      P=0.571      P=0.800      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart                                                                                                                            |
|     Cardiomyopathy                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     43/50 (86%)  48/50 (96%)  41/50 (82%)  46/50 (92%) |24/50 (48%)  19/50 (38%)  16/50 (32%)  21/50 (42%)  |
|POLY-3 ADJUSTED (b)|     89.9%        97.0%        84.8%        93.4%       |50.0%        42.3%        35.1%        46.0%        |
|TERMINAL (d)       |     25/25 (100%) 34/34 (100%) 31/35 (89%)  28/31 (90%) |19/38 (50%)  14/33 (42%)  10/34 (29%)  17/36 (47%)  |
|FIRST INCIDENCE    |     439          400          276          351         |438          599          325          549          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.460N     P=0.172N     P=0.015N*    P=0.308N    |P=0.491N     P=0.409N     P=0.179N     P=0.444N     |
|POLY 3             |     P=0.524      P=0.133      P=0.322N     P=0.391     |P=0.519N     P=0.295N     P=0.103N     P=0.428N     |
|POLY 1.5           |     P=0.497      P=0.127      P=0.320N     P=0.360     |P=0.511N     P=0.264N     P=0.094N     P=0.403N     |
|POLY 6             |     P=0.599N     P=0.153      P=0.312N     P=0.476     |P=0.522N     P=0.326N     P=0.111N     P=0.447N     |
|LOGISTIC REGRESSION|     P=0.445      P=0.145      P=0.319N     P=0.325     |P=0.510N     P=0.274N     P=0.073N     P=0.402N     |
|COCH-ARM / FISHERS |     P=0.420      P=0.080      P=0.393N     P=0.262     |P=0.485N     P=0.210N     P=0.076N     P=0.344N     |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 9
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart                                                                                                                            |
|     Thrombosis                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    1/50 (2%)    1/50 (2%)    3/50 (6%)   |0/50 (0%)    1/50 (2%)    2/50 (4%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     7.1%         2.2%         2.2%         6.9%        |0.0%         2.3%         4.6%         2.3%         |
|TERMINAL (d)       |     0/25 (0%)    1/34 (3%)    0/35 (0%)    1/31 (3%)   |0/38 (0%)    0/33 (0%)    1/34 (3%)    1/36 (3%)    |
|FIRST INCIDENCE    |     474          729 (T)      712          662         |---          617          696          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.430      P=0.256N     P=0.259N     P=0.614N    |P=0.495      P=0.482      P=0.217      P=0.489      |
|POLY 3             |     P=0.406      P=0.282N     P=0.287N     P=0.650N    |P=0.479      P=0.489      P=0.220      P=0.489      |
|POLY 1.5           |     P=0.410      P=0.290N     P=0.294N     P=0.653N    |P=0.486      P=0.493      P=0.225      P=0.493      |
|POLY 6             |     P=0.405      P=0.273N     P=0.274N     P=0.642N    |P=0.473      P=0.484      P=0.217      P=0.485      |
|LOGISTIC REGRESSION|     P=0.405      P=0.377N     P=0.349N     P=0.632     |P=0.499      P=0.567      P=0.222      P=0.489      |
|COCH-ARM / FISHERS |     P=0.414      P=0.309N     P=0.309N     P=0.661N    |P=0.500      P=0.500      P=0.247      P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Large, Rectum                                                                                                          |
|     Parasite Metazoan                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     10/50 (20%)  8/50 (16%)   7/50 (14%)   5/50 (10%)  |2/50 (4%)    5/50 (10%)   5/50 (10%)   4/50 (8%)    |
|POLY-3 ADJUSTED (b)|     24.0%        17.6%        15.8%        11.6%       |4.3%         11.5%        11.6%        9.1%         |
|TERMINAL (d)       |     8/25 (32%)   7/34 (21%)   7/35 (20%)   5/31 (16%)  |2/38 (5%)    5/33 (15%)   5/34 (15%)   4/36 (11%)   |
|FIRST INCIDENCE    |     549          641          729 (T)      729 (T)     |731 (T)      731 (T)      731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.088N     P=0.176N     P=0.103N     P=0.060N    |P=0.477      P=0.162      P=0.172      P=0.311      |
|POLY 3             |     P=0.125N     P=0.320N     P=0.246N     P=0.111N    |P=0.443      P=0.190      P=0.184      P=0.312      |
|POLY 1.5           |     P=0.123N     P=0.346N     P=0.265N     P=0.117N    |P=0.453      P=0.200      P=0.194      P=0.320      |
|POLY 6             |     P=0.126N     P=0.288N     P=0.215N     P=0.103N    |P=0.433      P=0.179      P=0.177      P=0.303      |
|LOGISTIC REGRESSION|     P=0.109N     P=0.292N     P=0.200N     P=0.096N    |P=0.477      P=0.162      P=0.172      P=0.311      |
|COCH-ARM / FISHERS |     P=0.123N     P=0.398N     P=0.298N     P=0.131N    |P=0.473      P=0.218      P=0.218      P=0.339      |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 10
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small, Ileum                                                                                                           |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    2/49 (4%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         4.6%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/25 (0%)    0/34 (0%)    1/35 (3%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          ---          662          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.693N     (e)          P=0.298      (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.695N     (e)          P=0.253      (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.695N     (e)          P=0.244      (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.693N     (e)          P=0.267      (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.696N     (e)          P=0.242      (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.697N     (e)          P=0.242      (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small, Jejunum                                                                                                         |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         4.5%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/25 (0%)    0/34 (0%)    2/35 (6%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          ---          729 (T)      ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.687N     (e)          P=0.315      (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.696N     (e)          P=0.256      (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.696N     (e)          P=0.248      (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.694N     (e)          P=0.268      (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          P=0.315      (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.697N     (e)          P=0.247      (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 11
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Accumulation, Hyaline Droplet                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |2/50 (4%)    0/50 (0%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |4.2%         0.0%         2.3%         0.0%         |
|TERMINAL (d)       |     0/25 (0%)    0/34 (0%)    0/35 (0%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |438          ---          724          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.278N     P=0.262N     P=0.541N     P=0.256N     |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.266N     P=0.256N     P=0.534N     P=0.254N     |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.268N     P=0.249N     P=0.524N     P=0.248N     |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.264N     P=0.264N     P=0.542N     P=0.260N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.244N     P=0.124N     P=0.395N     P=0.129N     |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.271N     P=0.247N     P=0.500N     P=0.247N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    1/50 (2%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         4.4%         2.2%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/25 (0%)    2/34 (6%)    0/35 (0%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          729 (T)      617          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.363N     P=0.308      P=0.523      (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.360N     P=0.259      P=0.518      (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.365N     P=0.252      P=0.511      (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.351N     P=0.270      P=0.530      (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.377N     P=0.308      P=0.476      (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.378N     P=0.247      P=0.500      (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 12
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     9/50 (18%)   25/50 (50%)  22/50 (44%)  18/50 (36%) |4/50 (8%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     21.1%        54.2%        48.5%        41.0%       |9.7%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     6/25 (24%)   22/34 (65%)  20/35 (57%)  15/31 (48%) |1/25 (4%)    0/34 (0%)    0/35 (0%)    0/31 (0%)    |
|FIRST INCIDENCE    |     439          474          474          603         |668          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.446      P=0.011 *    P=0.044 *    P=0.101     |P=0.073N     P=0.041N*    P=0.040N*    P=0.051N     |
|POLY 3             |     P=0.361      P<0.001 **   P=0.005 **   P=0.035 *   |P=0.082N     P=0.050N     P=0.051N     P=0.055N     |
|POLY 1.5           |     P=0.361      P<0.001 **   P=0.004 **   P=0.035 *   |P=0.079N     P=0.053N     P=0.055N     P=0.056N     |
|POLY 6             |     P=0.379      P<0.001 **   P=0.007 **   P=0.038 *   |P=0.086N     P=0.046N*    P=0.046N*    P=0.052N     |
|LOGISTIC REGRESSION|     P=0.366      P=0.002 **   P=0.007 **   P=0.044 *   |P=0.075N     P=0.052N     P=0.054N     P=0.056N     |
|COCH-ARM / FISHERS |     P=0.356      P<0.001 **   P=0.004 **   P=0.035 *   |P=0.077N     P=0.059N     P=0.059N     P=0.059N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Nephropathy                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     44/50 (88%)  48/50 (96%)  46/50 (92%)  47/50 (94%) |29/50 (58%)  27/50 (54%)  29/50 (58%)  25/50 (50%)  |
|POLY-3 ADJUSTED (b)|     94.4%        97.6%        92.9%        95.7%       |61.0%        58.7%        65.5%        53.4%        |
|TERMINAL (d)       |     25/25 (100%) 33/34 (97%)  35/35 (100%) 30/31 (97%) |24/38 (63%)  22/33 (67%)  24/34 (71%)  20/36 (56%)  |
|FIRST INCIDENCE    |     453          474          276          456         |589          505          434          246          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.469N     P=0.131N     P=0.048N*    P=0.286N    |P=0.275N     P=0.448      P=0.333      P=0.385N     |
|POLY 3             |     P=0.622      P=0.375      P=0.549N     P=0.581     |P=0.249N     P=0.491N     P=0.409      P=0.292N     |
|POLY 1.5           |     P=0.533      P=0.268      P=0.648N     P=0.449     |P=0.249N     P=0.465N     P=0.463      P=0.281N     |
|POLY 6             |     P=0.523N     P=0.567      P=0.452N     P=0.683N    |P=0.258N     P=0.523N     P=0.361      P=0.312N     |
|LOGISTIC REGRESSION|     P=0.402      P=0.340      P=0.485      P=0.339     |P=0.305N     P=0.539N     P=0.370      P=0.311N     |
|COCH-ARM / FISHERS |     P=0.363      P=0.134      P=0.370      P=0.243     |P=0.266N     P=0.420N     P=0.580N     P=0.274N     |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 13
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Pigmentation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    3/50 (6%)    1/50 (2%)   |3/50 (6%)    3/50 (6%)    2/50 (4%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         4.4%         6.7%         2.3%        |6.3%         6.8%         4.6%         0.0%         |
|TERMINAL (d)       |     0/25 (0%)    2/34 (6%)    2/35 (6%)    1/31 (3%)   |1/38 (3%)    1/33 (3%)    1/34 (3%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          729 (T)      722          729 (T)     |589          617          661          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.635N     P=0.308      P=0.187      P=0.543     |P=0.082N     P=0.606      P=0.547N     P=0.137N     |
|POLY 3             |     P=0.636      P=0.259      P=0.134      P=0.510     |P=0.080N     P=0.630      P=0.540N     P=0.132N     |
|POLY 1.5           |     P=0.631      P=0.252      P=0.128      P=0.507     |P=0.078N     P=0.642      P=0.528N     P=0.127N     |
|POLY 6             |     P=0.636N     P=0.270      P=0.145      P=0.516     |P=0.083N     P=0.616      P=0.551N     P=0.137N     |
|LOGISTIC REGRESSION|     P=0.639N     P=0.308      P=0.166      P=0.543     |P=0.071N     P=0.630N     P=0.473N     P=0.098N     |
|COCH-ARM / FISHERS |     P=0.618      P=0.247      P=0.121      P=0.500     |P=0.073N     P=0.661N     P=0.500N     P=0.121N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Angiectasis                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    4/50 (8%)    7/50 (14%)   4/49 (8%)   |0/50 (0%)    1/49 (2%)    2/48 (4%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     4.8%         8.9%         15.6%        9.5%        |0.0%         2.3%         4.7%         2.3%         |
|TERMINAL (d)       |     1/25 (4%)    4/34 (12%)   5/35 (14%)   4/31 (13%)  |0/38 (0%)    1/33 (3%)    2/34 (6%)    1/36 (3%)    |
|FIRST INCIDENCE    |     584          729 (T)      642          729 (T)     |---          731 (T)      731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.461      P=0.469      P=0.172      P=0.426     |P=0.502      P=0.472      P=0.214      P=0.489      |
|POLY 3             |     P=0.414      P=0.377      P=0.098      P=0.346     |P=0.481      P=0.486      P=0.216      P=0.489      |
|POLY 1.5           |     P=0.413      P=0.364      P=0.090      P=0.341     |P=0.488      P=0.490      P=0.219      P=0.493      |
|POLY 6             |     P=0.420      P=0.394      P=0.112      P=0.356     |P=0.475      P=0.481      P=0.214      P=0.485      |
|LOGISTIC REGRESSION|     P=0.416      P=0.378      P=0.096      P=0.353     |(e)          P=0.472      P=0.214      P=0.489      |
|COCH-ARM / FISHERS |     P=0.406      P=0.339      P=0.080      P=0.329     |P=0.503      P=0.495      P=0.237      P=0.500      |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 14
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Basophilic Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     26/50 (52%)  33/50 (66%)  35/50 (70%)  13/49 (27%) |43/50 (86%)  43/49 (88%)  35/48 (73%)  39/50 (78%)  |
|POLY-3 ADJUSTED (b)|     58.6%        71.0%        75.4%        30.8%       |89.4%        91.7%        77.4%        83.9%        |
|TERMINAL (d)       |     19/25 (76%)  28/34 (82%)  31/35 (89%)  13/31 (42%) |36/38 (95%)  33/33 (100%) 31/34 (91%)  33/36 (92%)  |
|FIRST INCIDENCE    |     439          536          464          729 (T)     |438          505          256          499          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001N**   P=0.504N     P=0.568      P<0.001N**  |P=0.191N     P=0.141      P=0.243N     P=0.434N     |
|POLY 3             |     P<0.001N**   P=0.146      P=0.060      P=0.006N**  |P=0.191N     P=0.489      P=0.082N     P=0.298N     |
|POLY 1.5           |     P<0.001N**   P=0.137      P=0.055      P=0.006N**  |P=0.179N     P=0.485      P=0.083N     P=0.277N     |
|POLY 6             |     P<0.001N**   P=0.167      P=0.075      P=0.006N**  |P=0.191N     P=0.510      P=0.082N     P=0.305N     |
|LOGISTIC REGRESSION|     P<0.001N**   P=0.216      P=0.083      P=0.004N**  |P=0.202N     P=0.337      P=0.139N     P=0.402N     |
|COCH-ARM / FISHERS |     P<0.001N**   P=0.111      P=0.050      P=0.008N**  |P=0.144N     P=0.516      P=0.087N     P=0.218N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Clear Cell Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     8/50 (16%)   16/50 (32%)  16/50 (32%)  4/49 (8%)   |4/50 (8%)    2/49 (4%)    1/48 (2%)    3/50 (6%)    |
|POLY-3 ADJUSTED (b)|     19.6%        35.5%        36.0%        9.5%        |8.6%         4.6%         2.4%         6.7%         |
|TERMINAL (d)       |     8/25 (32%)   16/34 (47%)  16/35 (46%)  4/31 (13%)  |4/38 (11%)   2/33 (6%)    1/34 (3%)    2/36 (6%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      729 (T)     |731 (T)      731 (T)      731 (T)      589          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.008N**   P=0.187      P=0.213      P=0.082N    |P=0.593N     P=0.403N     P=0.214N     P=0.532N     |
|POLY 3             |     P=0.017N*    P=0.077      P=0.070      P=0.158N    |P=0.591N     P=0.371N     P=0.209N     P=0.525N     |
|POLY 1.5           |     P=0.019N*    P=0.066      P=0.061      P=0.168N    |P=0.591N     P=0.361N     P=0.204N     P=0.517N     |
|POLY 6             |     P=0.014N*    P=0.093      P=0.091      P=0.143N    |P=0.590N     P=0.382N     P=0.212N     P=0.531N     |
|LOGISTIC REGRESSION|     P=0.008N**   P=0.187      P=0.213      P=0.082N    |P=0.606N     P=0.403N     P=0.214N     P=0.519N     |
|COCH-ARM / FISHERS |     P=0.028N*    P=0.050      P=0.050      P=0.188N    |P=0.588N     P=0.349N     P=0.194N     P=0.500N     |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 15
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Degeneration Cystic                                                                                                         |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    7/50 (14%)   5/50 (10%)   6/49 (12%)  |1/50 (2%)    0/49 (0%)    1/48 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     7.2%         15.3%        11.1%        14.2%       |2.1%         0.0%         2.4%         0.0%         |
|TERMINAL (d)       |     1/25 (4%)    5/34 (15%)   3/35 (9%)    5/31 (16%)  |1/38 (3%)    0/33 (0%)    1/34 (3%)    0/36 (0%)    |
|FIRST INCIDENCE    |     474          589          617          710         |731 (T)      ---          731 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.419      P=0.280      P=0.495      P=0.340     |P=0.463N     P=0.528N     P=0.737      P=0.511N     |
|POLY 3             |     P=0.372      P=0.199      P=0.399      P=0.248     |P=0.464N     P=0.514N     P=0.739      P=0.511N     |
|POLY 1.5           |     P=0.372      P=0.184      P=0.381      P=0.244     |P=0.464N     P=0.510N     P=0.742      P=0.507N     |
|POLY 6             |     P=0.376      P=0.221      P=0.430      P=0.260     |P=0.463N     P=0.519N     P=0.737      P=0.515N     |
|LOGISTIC REGRESSION|     P=0.370      P=0.153      P=0.355      P=0.252     |P=0.463N     (e)          P=0.737      (e)          |
|COCH-ARM / FISHERS |     P=0.366      P=0.159      P=0.357      P=0.233     |P=0.462N     P=0.505N     P=0.742      P=0.500N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Eosinophilic Focus                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     10/50 (20%)  8/50 (16%)   9/50 (18%)   7/49 (14%)  |0/50 (0%)    0/49 (0%)    3/48 (6%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     23.9%        17.6%        19.9%        16.4%       |0.0%         0.0%         7.0%         0.0%         |
|TERMINAL (d)       |     8/25 (32%)   7/34 (21%)   7/35 (20%)   6/31 (19%)  |0/38 (0%)    0/33 (0%)    2/34 (6%)    0/36 (0%)    |
|FIRST INCIDENCE    |     453          641          474          603         |---          ---          470          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.252N     P=0.177N     P=0.240N     P=0.166N    |P=0.646N     (e)          P=0.107      (e)          |
|POLY 3             |     P=0.324N     P=0.324N     P=0.426N     P=0.278N    |P=0.665N     (e)          P=0.105      (e)          |
|POLY 1.5           |     P=0.323N     P=0.349N     P=0.456N     P=0.290N    |P=0.660N     (e)          P=0.107      (e)          |
|POLY 6             |     P=0.320N     P=0.290N     P=0.380N     P=0.257N    |P=0.669N     (e)          P=0.104      (e)          |
|LOGISTIC REGRESSION|     P=0.314N     P=0.314N     P=0.451N     P=0.272N    |P=0.622N     (e)          P=0.139      (e)          |
|COCH-ARM / FISHERS |     P=0.324N     P=0.398N     P=0.500N     P=0.314N    |P=0.647N     (e)          P=0.114      (e)          |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 16
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Fatty Change                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     23/50 (46%)  18/50 (36%)  21/50 (42%)  9/49 (18%)  |21/50 (42%)  13/49 (27%)  11/48 (23%)  7/50 (14%)   |
|POLY-3 ADJUSTED (b)|     50.8%        38.7%        44.9%        20.5%       |45.1%        28.9%        26.0%        15.4%        |
|TERMINAL (d)       |     15/25 (60%)  13/34 (38%)  18/35 (51%)  5/31 (16%)  |21/38 (55%)  11/33 (33%)  11/34 (32%)  4/36 (11%)   |
|FIRST INCIDENCE    |     38           474          276          530         |731 (T)      328          731 (T)      527          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.002N**   P=0.043N*    P=0.089N     P<0.001N**  |P=0.004N**   P=0.143N     P=0.044N*    P=0.003N**   |
|POLY 3             |     P=0.003N**   P=0.165N     P=0.358N     P=0.002N**  |P=0.003N**   P=0.080N     P=0.046N*    P<0.001N**   |
|POLY 1.5           |     P=0.003N**   P=0.186N     P=0.389N     P=0.002N**  |P=0.004N**   P=0.078N     P=0.043N*    P<0.001N**   |
|POLY 6             |     P=0.002N**   P=0.134N     P=0.308N     P<0.001N**  |P=0.003N**   P=0.085N     P=0.047N*    P<0.001N**   |
|LOGISTIC REGRESSION|     P=0.004N**   P=0.242N     P=0.465N     P=0.004N**  |P=0.005N**   P=0.097N     P=0.044N*    P=0.003N**   |
|COCH-ARM / FISHERS |     P=0.003N**   P=0.208N     P=0.420N     P=0.003N**  |P=0.004N**   P=0.079N     P=0.036N*    P=0.002N**   |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hepatodiaphragmatic Nodule                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     8/50 (16%)   5/50 (10%)   9/50 (18%)   6/49 (12%)  |9/50 (18%)   7/49 (14%)   8/48 (17%)   12/50 (24%)  |
|POLY-3 ADJUSTED (b)|     19.3%        11.1%        19.2%        14.1%       |19.1%        15.5%        18.5%        25.4%        |
|TERMINAL (d)       |     4/25 (16%)   4/34 (12%)   5/35 (14%)   5/31 (16%)  |7/38 (18%)   4/33 (12%)   7/34 (21%)   6/36 (17%)   |
|FIRST INCIDENCE    |     629          716          464          662         |616          328          325          500          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.417N     P=0.139N     P=0.496N     P=0.264N    |P=0.165      P=0.496N     P=0.596N     P=0.275      |
|POLY 3             |     P=0.481N     P=0.223N     P=0.606N     P=0.367N    |P=0.173      P=0.428N     P=0.575N     P=0.313      |
|POLY 1.5           |     P=0.478N     P=0.240N     P=0.566      P=0.378N    |P=0.166      P=0.419N     P=0.563N     P=0.309      |
|POLY 6             |     P=0.481N     P=0.203N     P=0.555N     P=0.351N    |P=0.184      P=0.443N     P=0.588N     P=0.321      |
|LOGISTIC REGRESSION|     P=0.474N     P=0.191N     P=0.486      P=0.343N    |P=0.193      P=0.354N     P=0.538N     P=0.379      |
|COCH-ARM / FISHERS |     P=0.477N     P=0.277N     P=0.500      P=0.403N    |P=0.164      P=0.410N     P=0.537N     P=0.312      |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 17
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     8/50 (16%)   21/50 (42%)  29/50 (58%)  10/49 (20%) |8/50 (16%)   0/50 (0%)    0/50 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     19.4%        44.9%        63.2%        23.7%       |19.1%        0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     7/25 (28%)   16/34 (47%)  27/35 (77%)  10/31 (32%) |6/25 (24%)   0/34 (0%)    0/35 (0%)    0/31 (0%)    |
|FIRST INCIDENCE    |     639          474          464          729 (T)     |453          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.115N     P=0.036 *    P<0.001 **   P=0.595     |P=0.008N**   P=0.002N**   P<0.001N**   P=0.002N**   |
|POLY 3             |     P=0.182N     P=0.008 **   P<0.001 **   P=0.418     |P=0.008N**   P=0.002N**   P=0.003N**   P=0.003N**   |
|POLY 1.5           |     P=0.183N     P=0.006 **   P<0.001 **   P=0.406     |P=0.008N**   P=0.003N**   P=0.003N**   P=0.003N**   |
|POLY 6             |     P=0.175N     P=0.013 *    P<0.001 **   P=0.439     |P=0.009N**   P=0.002N**   P=0.002N**   P=0.003N**   |
|LOGISTIC REGRESSION|     P=0.194N     P=0.009 **   P<0.001 **   P=0.505     |P=0.010N*    P=0.004N**   P=0.004N**   P=0.005N**   |
|COCH-ARM / FISHERS |     P=0.215N     P=0.004 **   P<0.001 **   P=0.379     |P=0.010N*    P=0.003N**   P=0.003N**   P=0.003N**   |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Mixed Cell Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     16/50 (32%)  23/50 (46%)  22/50 (44%)  10/49 (20%) |2/50 (4%)    7/49 (14%)   8/48 (17%)   5/50 (10%)   |
|POLY-3 ADJUSTED (b)|     38.9%        51.0%        49.5%        23.7%       |4.3%         15.9%        18.9%        11.3%        |
|TERMINAL (d)       |     15/25 (60%)  23/34 (68%)  22/35 (63%)  10/31 (32%) |1/38 (3%)    6/33 (18%)   8/34 (24%)   5/36 (14%)   |
|FIRST INCIDENCE    |     668          729 (T)      729 (T)      729 (T)     |719          527          731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.002N**   P=0.488      P=0.577N     P=0.023N*   |P=0.468      P=0.057      P=0.031 *    P=0.195      |
|POLY 3             |     P=0.013N*    P=0.174      P=0.216      P=0.098N    |P=0.425      P=0.065      P=0.031 *    P=0.194      |
|POLY 1.5           |     P=0.015N*    P=0.150      P=0.187      P=0.111N    |P=0.441      P=0.069      P=0.033 *    P=0.201      |
|POLY 6             |     P=0.010N*    P=0.212      P=0.272      P=0.081N    |P=0.410      P=0.061      P=0.029 *    P=0.186      |
|LOGISTIC REGRESSION|     P=0.003N**   P=0.340      P=0.493      P=0.041N*   |P=0.440      P=0.071      P=0.028 *    P=0.183      |
|COCH-ARM / FISHERS |     P=0.023N*    P=0.109      P=0.151      P=0.140N    |P=0.473      P=0.075      P=0.039 *    P=0.218      |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 18
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    1/50 (2%)    0/50 (0%)    3/49 (6%)   |2/50 (4%)    3/49 (6%)    1/48 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     9.6%         2.2%         0.0%         6.9%        |4.3%         6.8%         2.4%         0.0%         |
|TERMINAL (d)       |     1/25 (4%)    0/34 (0%)    0/35 (0%)    0/31 (0%)   |1/38 (3%)    0/33 (0%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     549          716          ---          466         |616          505          711          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.549      P=0.134N     P=0.045N*    P=0.449N    |P=0.115N     P=0.458      P=0.543N     P=0.258N     |
|POLY 3             |     P=0.521      P=0.156N     P=0.053N     P=0.480N    |P=0.113N     P=0.474      P=0.535N     P=0.252N     |
|POLY 1.5           |     P=0.524      P=0.163N     P=0.056N     P=0.490N    |P=0.109N     P=0.481      P=0.530N     P=0.247N     |
|POLY 6             |     P=0.519      P=0.147N     P=0.048N*    P=0.465N    |P=0.116N     P=0.467      P=0.540N     P=0.257N     |
|LOGISTIC REGRESSION|     P=0.513      P=0.185N     P=0.065N     P=0.547N    |P=0.089N     P=0.577      P=0.499N     P=0.213N     |
|COCH-ARM / FISHERS |     P=0.528      P=0.181N     P=0.059N     P=0.511N    |P=0.104N     P=0.490      P=0.515N     P=0.247N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Thrombosis                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    0/50 (0%)    0/49 (0%)   |2/50 (4%)    0/49 (0%)    3/48 (6%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         2.2%         0.0%         0.0%        |4.2%         0.0%         7.1%         0.0%         |
|TERMINAL (d)       |     0/25 (0%)    1/34 (3%)    0/35 (0%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    1/34 (3%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          729 (T)      ---          ---         |616          ---          704          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.567N     P=0.561      (e)          (e)         |P=0.309N     P=0.273N     P=0.443      P=0.266N     |
|POLY 3             |     P=0.566N     P=0.519      (e)          (e)         |P=0.304N     P=0.256N     P=0.454      P=0.252N     |
|POLY 1.5           |     P=0.571N     P=0.513      (e)          (e)         |P=0.301N     P=0.250N     P=0.461      P=0.247N     |
|POLY 6             |     P=0.560N     P=0.528      (e)          (e)         |P=0.306N     P=0.263N     P=0.448      P=0.258N     |
|LOGISTIC REGRESSION|     (e)          P=0.561      (e)          (e)         |P=0.296N     P=0.212N     P=0.483      P=0.207N     |
|COCH-ARM / FISHERS |     P=0.580N     P=0.500      (e)          (e)         |P=0.295N     P=0.253N     P=0.480      P=0.247N     |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 19
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Vacuolization Cytoplasmic                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     14/50 (28%)  18/50 (36%)  23/50 (46%)  28/49 (57%) |7/50 (14%)   14/49 (29%)  17/48 (35%)  30/50 (60%)  |
|POLY-3 ADJUSTED (b)|     32.8%        39.9%        51.5%        64.7%       |14.9%        31.7%        40.0%        67.2%        |
|TERMINAL (d)       |     9/25 (36%)   18/34 (53%)  22/35 (63%)  25/31 (81%) |5/38 (13%)   12/33 (36%)  16/34 (47%)  29/36 (81%)  |
|FIRST INCIDENCE    |     453          729 (T)      662          533         |616          609          696          553          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.003 **   P=0.549N     P=0.297      P=0.025 *   |P<0.001 **   P=0.036 *    P=0.007 **   P<0.001 **   |
|POLY 3             |     P<0.001 **   P=0.315      P=0.055      P=0.002 **  |P<0.001 **   P=0.047 *    P=0.006 **   P<0.001 **   |
|POLY 1.5           |     P<0.001 **   P=0.300      P=0.051      P=0.002 **  |P<0.001 **   P=0.052      P=0.007 **   P<0.001 **   |
|POLY 6             |     P<0.001 **   P=0.336      P=0.067      P=0.002 **  |P<0.001 **   P=0.041 *    P=0.005 **   P<0.001 **   |
|LOGISTIC REGRESSION|     P=0.002 **   P=0.401      P=0.092      P=0.005 **  |P<0.001 **   P=0.050      P=0.007 **   P<0.001 **   |
|COCH-ARM / FISHERS |     P=0.002 **   P=0.260      P=0.048 *    P=0.003 **  |P<0.001 **   P=0.063      P=0.012 *    P<0.001 **   |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Bile Duct                                                                                                                 |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     42/50 (84%)  48/50 (96%)  48/50 (96%)  36/49 (73%) |14/50 (28%)  5/49 (10%)   13/48 (27%)  9/50 (18%)   |
|POLY-3 ADJUSTED (b)|     89.5%        97.9%        98.4%        77.8%       |29.9%        11.4%        29.6%        19.7%        |
|TERMINAL (d)       |     23/25 (92%)  34/34 (100%) 35/35 (100%) 23/31 (74%) |10/38 (26%)  3/33 (9%)    8/34 (24%)   4/36 (11%)   |
|FIRST INCIDENCE    |     453          474          464          530         |716          690          434          500          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.019N*    P=0.233N     P=0.192N     P=0.036N*   |P=0.419N     P=0.052N     P=0.540      P=0.233N     |
|POLY 3             |     P<0.001N**   P=0.076      P=0.058      P=0.094N    |P=0.386N     P=0.026N*    P=0.579N     P=0.183N     |
|POLY 1.5           |     P<0.001N**   P=0.066      P=0.051      P=0.103N    |P=0.393N     P=0.024N*    P=0.576N     P=0.181N     |
|POLY 6             |     P<0.001N**   P=0.106      P=0.079      P=0.075N    |P=0.373N     P=0.029N*    P=0.573N     P=0.183N     |
|LOGISTIC REGRESSION|     P=0.003N**   P=0.121      P=0.069      P=0.093N    |P=0.411N     P=0.035N*    P=0.587      P=0.182N     |
|COCH-ARM / FISHERS |     P=0.005N**   P=0.046 *    P=0.046 *    P=0.150N    |P=0.396N     P=0.022N*    P=0.550N     P=0.171N     |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 20
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Congestion                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    2/50 (4%)    1/50 (2%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         4.3%         2.2%         0.0%        |0.0%         0.0%         2.3%         0.0%         |
|TERMINAL (d)       |     0/25 (0%)    0/34 (0%)    0/35 (0%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          536          662          ---         |---          ---          508          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.380N     P=0.260      P=0.535      (e)         |P=0.787N     (e)          P=0.483      (e)          |
|POLY 3             |     P=0.359N     P=0.265      P=0.518      (e)         |P=0.790N     (e)          P=0.487      (e)          |
|POLY 1.5           |     P=0.365N     P=0.255      P=0.510      (e)         |P=0.789N     (e)          P=0.491      (e)          |
|POLY 6             |     P=0.350N     P=0.279      P=0.529      (e)         |P=0.791N     (e)          P=0.484      (e)          |
|LOGISTIC REGRESSION|     P=0.408N     P=0.144      P=0.494      (e)         |P=0.755N     (e)          P=0.693      (e)          |
|COCH-ARM / FISHERS |     P=0.378N     P=0.247      P=0.500      (e)         |P=0.786N     (e)          P=0.500      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Hemorrhage                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    0/50 (0%)    2/50 (4%)    0/50 (0%)   |0/50 (0%)    1/50 (2%)    2/50 (4%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     9.4%         0.0%         4.3%         0.0%        |0.0%         2.3%         4.5%         0.0%         |
|TERMINAL (d)       |     0/25 (0%)    0/34 (0%)    0/35 (0%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     453          ---          276          ---         |---          540          470          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.111N     P=0.055N     P=0.311N     P=0.059N    |P=0.515N     P=0.492      P=0.229      (e)          |
|POLY 3             |     P=0.117N     P=0.053N     P=0.302N     P=0.059N    |P=0.533N     P=0.490      P=0.227      (e)          |
|POLY 1.5           |     P=0.114N     P=0.055N     P=0.314N     P=0.059N    |P=0.527N     P=0.493      P=0.229      (e)          |
|POLY 6             |     P=0.120N     P=0.051N     P=0.286N     P=0.058N    |P=0.539N     P=0.485      P=0.225      (e)          |
|LOGISTIC REGRESSION|     P=0.139N     P=0.094N     P=0.454N     P=0.080N    |P=0.406N     P=0.640      P=0.490      (e)          |
|COCH-ARM / FISHERS |     P=0.111N     P=0.059N     P=0.339N     P=0.059N    |P=0.515N     P=0.500      P=0.247      (e)          |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 21
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    3/50 (6%)    4/50 (8%)    6/50 (12%)  |5/50 (10%)   4/50 (8%)    4/50 (8%)    4/50 (8%)    |
|POLY-3 ADJUSTED (b)|     4.8%         6.6%         9.0%         13.8%       |10.6%        9.0%         9.3%         9.1%         |
|TERMINAL (d)       |     1/25 (4%)    2/34 (6%)    3/35 (9%)    4/31 (13%)  |2/38 (5%)    3/33 (9%)    3/34 (9%)    4/36 (11%)   |
|FIRST INCIDENCE    |     439          696          722          618         |616          540          724          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.109      P=0.602      P=0.470      P=0.202     |P=0.498N     P=0.575N     P=0.571N     P=0.543N     |
|POLY 3             |     P=0.094      P=0.537      P=0.367      P=0.145     |P=0.519N     P=0.542N     P=0.559N     P=0.544N     |
|POLY 1.5           |     P=0.094      P=0.524      P=0.355      P=0.142     |P=0.509N     P=0.526N     P=0.540N     P=0.528N     |
|POLY 6             |     P=0.096      P=0.555      P=0.389      P=0.154     |P=0.529N     P=0.561N     P=0.577N     P=0.561N     |
|LOGISTIC REGRESSION|     P=0.093      P=0.474      P=0.338      P=0.136     |P=0.507N     P=0.476N     P=0.535N     P=0.522N     |
|COCH-ARM / FISHERS |     P=0.092      P=0.500      P=0.339      P=0.134     |P=0.494N     P=0.500N     P=0.500N     P=0.500N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung: Alveolar Epithelium                                                                                                        |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    8/50 (16%)   6/50 (12%)   4/50 (8%)   |6/50 (12%)   3/50 (6%)    4/50 (8%)    6/50 (12%)   |
|POLY-3 ADJUSTED (b)|     7.3%         17.6%        13.5%        9.2%        |12.9%        6.9%         9.3%         13.6%        |
|TERMINAL (d)       |     3/25 (12%)   6/34 (18%)   6/35 (17%)   3/31 (10%)  |5/38 (13%)   3/33 (9%)    4/34 (12%)   6/36 (17%)   |
|FIRST INCIDENCE    |     729 (T)      681          729 (T)      645         |718          731 (T)      731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.362N     P=0.218      P=0.428      P=0.608     |P=0.382      P=0.317N     P=0.444N     P=0.580      |
|POLY 3             |     P=0.381N     P=0.133      P=0.284      P=0.532     |P=0.368      P=0.276N     P=0.422N     P=0.580      |
|POLY 1.5           |     P=0.389N     P=0.120      P=0.267      P=0.521     |P=0.372      P=0.263N     P=0.406N     P=0.594      |
|POLY 6             |     P=0.367N     P=0.153      P=0.312      P=0.550     |P=0.364      P=0.291N     P=0.435N     P=0.567      |
|LOGISTIC REGRESSION|     P=0.389N     P=0.164      P=0.428      P=0.551     |P=0.370      P=0.313N     P=0.450N     P=0.565      |
|COCH-ARM / FISHERS |     P=0.408N     P=0.100      P=0.243      P=0.500     |P=0.380      P=0.243N     P=0.370N     P=0.620N     |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 22
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mandibular                                                                                                           |
|     Ectasia                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/49 (2%)    4/50 (8%)    1/49 (2%)    4/49 (8%)   |1/50 (2%)    1/49 (2%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     2.5%         8.8%         2.3%         9.4%        |2.1%         2.3%         0.0%         2.3%         |
|TERMINAL (d)       |     0/25 (0%)    3/34 (9%)    1/34 (3%)    3/31 (10%)  |1/38 (3%)    0/32 (0%)    0/34 (0%)    1/36 (3%)    |
|FIRST INCIDENCE    |     716          589          729 (T)      680         |731 (T)      721          ---          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.271      P=0.267      P=0.694N     P=0.244     |P=0.677      P=0.729      P=0.522N     P=0.750      |
|POLY 3             |     P=0.258      P=0.218      P=0.744N     P=0.196     |P=0.671      P=0.741      P=0.516N     P=0.748      |
|POLY 1.5           |     P=0.254      P=0.206      P=0.750N     P=0.190     |P=0.674      P=0.746      P=0.511N     P=0.752      |
|POLY 6             |     P=0.266      P=0.233      P=0.733N     P=0.205     |P=0.670      P=0.734      P=0.520N     P=0.744      |
|LOGISTIC REGRESSION|     P=0.249      P=0.202      P=0.725N     P=0.206     |P=0.671      P=0.732      (e)          P=0.750      |
|COCH-ARM / FISHERS |     P=0.244      P=0.187      P=0.753N     P=0.181     |P=0.679      P=0.747      P=0.500N     P=0.753N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mandibular                                                                                                           |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/49 (6%)    1/50 (2%)    0/49 (0%)    2/49 (4%)   |0/50 (0%)    0/49 (0%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     7.3%         2.2%         0.0%         4.7%        |0.0%         0.0%         2.3%         0.0%         |
|TERMINAL (d)       |     1/25 (4%)    0/34 (0%)    0/34 (0%)    0/31 (0%)   |0/38 (0%)    0/32 (0%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     617          697          ---          662         |---          ---          711          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.611N     P=0.242N     P=0.092N     P=0.450N    |P=0.792N     (e)          P=0.469      (e)          |
|POLY 3             |     P=0.631N     P=0.271N     P=0.108N     P=0.479N    |P=0.788N     (e)          P=0.484      (e)          |
|POLY 1.5           |     P=0.628N     P=0.279N     P=0.112N     P=0.485N    |P=0.787N     (e)          P=0.489      (e)          |
|POLY 6             |     P=0.634N     P=0.261N     P=0.102N     P=0.469N    |P=0.789N     (e)          P=0.481      (e)          |
|LOGISTIC REGRESSION|     P=0.627N     P=0.311N     P=0.125N     P=0.510N    |P=0.787N     (e)          P=0.488      (e)          |
|COCH-ARM / FISHERS |     P=0.622N     P=0.301N     P=0.121N     P=0.500N    |P=0.785N     (e)          P=0.500      (e)          |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 23
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mesenteric                                                                                                           |
|     Ectasia                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    3/50 (6%)    1/50 (2%)    4/50 (8%)   |0/50 (0%)    1/50 (2%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     4.9%         6.6%         2.2%         9.3%        |0.0%         2.3%         0.0%         2.3%         |
|TERMINAL (d)       |     1/25 (4%)    2/34 (6%)    0/35 (0%)    4/31 (13%)  |0/38 (0%)    1/33 (3%)    0/34 (0%)    1/36 (3%)    |
|FIRST INCIDENCE    |     724          697          662          729 (T)     |---          731 (T)      ---          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.298      P=0.620      P=0.411N     P=0.436     |P=0.465      P=0.472      (e)          P=0.489      |
|POLY 3             |     P=0.280      P=0.545      P=0.469N     P=0.361     |P=0.450      P=0.487      (e)          P=0.489      |
|POLY 1.5           |     P=0.280      P=0.529      P=0.482N     P=0.353     |P=0.454      P=0.492      (e)          P=0.493      |
|POLY 6             |     P=0.281      P=0.566      P=0.450N     P=0.373     |P=0.445      P=0.481      (e)          P=0.485      |
|LOGISTIC REGRESSION|     P=0.280      P=0.584      P=0.472N     P=0.423     |(e)          P=0.472      (e)          P=0.489      |
|COCH-ARM / FISHERS |     P=0.275      P=0.500      P=0.500N     P=0.339     |P=0.464      P=0.500      (e)          P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mesenteric                                                                                                           |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         4.5%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/25 (0%)    0/34 (0%)    1/35 (3%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          ---          662          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.693N     (e)          P=0.298      (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.696N     (e)          P=0.257      (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.696N     (e)          P=0.249      (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.693N     (e)          P=0.271      (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.697N     (e)          P=0.246      (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.697N     (e)          P=0.247      (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 24
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Galactocele                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/46 (0%)    5/50 (10%)   0/49 (0%)    1/49 (2%)   |13/50 (26%)  9/50 (18%)   9/50 (18%)   9/50 (18%)   |
|POLY-3 ADJUSTED (b)|     0.0%         10.9%        0.0%         2.4%        |27.6%        20.0%        20.7%        20.1%        |
|TERMINAL (d)       |     0/22 (0%)    1/34 (3%)    0/34 (0%)    1/31 (3%)   |10/38 (26%)  5/33 (15%)   8/34 (24%)   8/36 (22%)   |
|FIRST INCIDENCE    |     ---          592          ---          729 (T)     |679          599          603          527          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.350N     P=0.062      (e)          P=0.568     |P=0.321N     P=0.358N     P=0.336N     P=0.286N     |
|POLY 3             |     P=0.319N     P=0.052      (e)          P=0.525     |P=0.334N     P=0.268N     P=0.302N     P=0.275N     |
|POLY 1.5           |     P=0.331N     P=0.047 *    (e)          P=0.521     |P=0.325N     P=0.257N     P=0.281N     P=0.261N     |
|POLY 6             |     P=0.302N     P=0.060      (e)          P=0.532     |P=0.346N     P=0.279N     P=0.320N     P=0.292N     |
|LOGISTIC REGRESSION|     P=0.357N     P=0.038 *    (e)          P=0.568     |P=0.330N     P=0.259N     P=0.312N     P=0.279N     |
|COCH-ARM / FISHERS |     P=0.358N     P=0.035 *    (e)          P=0.516     |P=0.309N     P=0.235N     P=0.235N     P=0.235N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/46 (4%)    3/50 (6%)    4/49 (8%)    4/49 (8%)   |8/50 (16%)   11/50 (22%)  9/50 (18%)   6/50 (12%)   |
|POLY-3 ADJUSTED (b)|     5.4%         6.7%         9.2%         9.4%        |17.1%        24.6%        20.9%        13.6%        |
|TERMINAL (d)       |     2/22 (9%)    3/34 (9%)    4/34 (12%)   3/31 (10%)  |6/38 (16%)   7/33 (21%)   8/34 (24%)   4/36 (11%)   |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      726         |674          609          711          707          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.384      P=0.671N     P=0.550      P=0.495     |P=0.212N     P=0.213      P=0.396      P=0.438N     |
|POLY 3             |     P=0.344      P=0.586      P=0.409      P=0.397     |P=0.230N     P=0.263      P=0.423      P=0.433N     |
|POLY 1.5           |     P=0.341      P=0.569      P=0.392      P=0.387     |P=0.219N     P=0.278      P=0.447      P=0.417N     |
|POLY 6             |     P=0.350      P=0.607      P=0.436      P=0.414     |P=0.242N     P=0.249      P=0.403      P=0.450N     |
|LOGISTIC REGRESSION|     P=0.384      P=0.671N     P=0.550      P=0.488     |P=0.221N     P=0.262      P=0.403      P=0.446N     |
|COCH-ARM / FISHERS |     P=0.333      P=0.540      P=0.369      P=0.369     |P=0.199N     P=0.306      P=0.500      P=0.387N     |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 25
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery: Fat                                                                                                                   |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     6/13 (46%)   12/13 (92%)  11/11 (100%) 9/12 (75%)  |2/13 (15%)   0/13 (0%)    0/11 (0%)    0/12 (0%)    |
|POLY-3 ADJUSTED (b)|     52.1%        92.3%        100.0%       77.8%       |17.7%        0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     5/6 (83%)    10/11 (91%)  9/9 (100%)   8/10 (80%)  |1/6 (17%)    0/11 (0%)    0/9 (0%)     0/10 (0%)    |
|FIRST INCIDENCE    |     629          641          688          645         |701          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.342N     P=0.445      P=0.319      P=0.622N    |P=0.221N     P=0.157N     P=0.172N     P=0.172N     |
|POLY 3             |     P=0.466      P=0.022 *    P=0.004 **   P=0.187     |P=0.266N     P=0.205N     P=0.240N     P=0.228N     |
|POLY 1.5           |     P=0.426      P=0.015 *    P=0.003 **   P=0.168     |P=0.259N     P=0.215N     P=0.251N     P=0.236N     |
|POLY 6             |     P=0.511      P=0.037 *    P=0.007 **   P=0.216     |P=0.275N     P=0.195N     P=0.227N     P=0.219N     |
|LOGISTIC REGRESSION|     P=0.448      P=0.038 *    P=0.021 *    P=0.221     |P=0.246N     P=0.197N     P=0.230N     P=0.220N     |
|COCH-ARM / FISHERS |     P=0.371      P=0.015 *    P=0.005 **   P=0.144     |P=0.253N     P=0.240N     P=0.283N     P=0.260N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery: Fat                                                                                                                   |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/13 (8%)    1/13 (8%)    0/11 (0%)    1/12 (8%)   |1/7 (14%)    1/2 (50%)    4/8 (50%)    2/4 (50%)    |
|POLY-3 ADJUSTED (b)|     8.9%         8.0%         0.0%         8.6%        |14.6%        50.0%        57.6%        58.3%        |
|TERMINAL (d)       |     0/6 (0%)     1/11 (9%)    0/9 (0%)     0/10 (0%)   |0/5 (0%)     0/1 (0%)     2/3 (67%)    2/3 (67%)    |
|FIRST INCIDENCE    |     716          729 (T)      ---          603         |514          505          603          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.678N     P=0.671N     P=0.455N     P=0.735N    |P=0.379      P=0.749      P=0.110      P=0.368      |
|POLY 3             |     P=0.673      P=0.737N     P=0.509N     P=0.752N    |P=0.194      P=0.465      P=0.125      P=0.237      |
|POLY 1.5           |     P=0.667      P=0.746N     P=0.519N     P=0.760     |P=0.227      P=0.463      P=0.144      P=0.256      |
|POLY 6             |     P=0.682      P=0.725N     P=0.498N     P=0.738N    |P=0.161      P=0.470      P=0.106      P=0.217      |
|LOGISTIC REGRESSION|     P=0.625      P=0.721N     P=0.503N     P=0.704     |P=0.261      (e)          P=0.209      P=0.291      |
|COCH-ARM / FISHERS |     P=0.661      P=0.760N     P=0.542N     P=0.740     |P=0.271      P=0.417      P=0.182      P=0.279      |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 26
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose                                                                                                                             |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    7/50 (14%)   6/49 (12%)   6/50 (12%)  |3/50 (6%)    0/50 (0%)    0/49 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     7.2%         15.2%        13.5%        13.9%       |7.3%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/25 (4%)    4/34 (12%)   6/35 (17%)   4/31 (13%)  |0/25 (0%)    0/34 (0%)    0/35 (0%)    0/31 (0%)    |
|FIRST INCIDENCE    |     563          589          729 (T)      680         |674          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.429      P=0.273      P=0.396      P=0.334     |P=0.127N     P=0.092N     P=0.088N     P=0.103N     |
|POLY 3             |     P=0.395      P=0.199      P=0.272      P=0.259     |P=0.145N     P=0.103N     P=0.106N     P=0.111N     |
|POLY 1.5           |     P=0.397      P=0.184      P=0.258      P=0.255     |P=0.140N     P=0.108N     P=0.112N     P=0.113N     |
|POLY 6             |     P=0.396      P=0.219      P=0.293      P=0.267     |P=0.151N     P=0.098N     P=0.099N     P=0.107N     |
|LOGISTIC REGRESSION|     P=0.395      P=0.150      P=0.265      P=0.259     |P=0.133N     P=0.108N     P=0.112N     P=0.113N     |
|COCH-ARM / FISHERS |     P=0.390      P=0.159      P=0.233      P=0.243     |P=0.135N     P=0.121N     P=0.125N     P=0.121N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose                                                                                                                             |
|     Thrombosis                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    1/50 (2%)    0/49 (0%)    1/50 (2%)   |0/50 (0%)    3/50 (6%)    1/50 (2%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     4.9%         2.2%         0.0%         2.3%        |0.0%         6.8%         2.3%         4.4%         |
|TERMINAL (d)       |     0/25 (0%)    1/34 (3%)    0/35 (0%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    1/34 (3%)    0/36 (0%)    |
|FIRST INCIDENCE    |     710          729 (T)      ---          456         |---          617          731 (T)      553          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.484N     P=0.414N     P=0.184N     P=0.457N    |P=0.427      P=0.106      P=0.478      P=0.223      |
|POLY 3             |     P=0.506N     P=0.467N     P=0.220N     P=0.477N    |P=0.422      P=0.110      P=0.484      P=0.230      |
|POLY 1.5           |     P=0.503N     P=0.478N     P=0.228N     P=0.484N    |P=0.426      P=0.113      P=0.489      P=0.232      |
|POLY 6             |     P=0.510N     P=0.453N     P=0.209N     P=0.466N    |P=0.420      P=0.106      P=0.480      P=0.229      |
|LOGISTIC REGRESSION|     P=0.510N     P=0.437N     P=0.204N     P=0.531N    |P=0.460      P=0.132      P=0.478      P=0.330      |
|COCH-ARM / FISHERS |     P=0.500N     P=0.500N     P=0.253N     P=0.500N    |P=0.437      P=0.121      P=0.500      P=0.247      |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 27
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose: Olfactory Epithelium                                                                                                       |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/49 (0%)    48/50 (96%) |0/50 (0%)    0/50 (0%)    1/50 (2%)    19/50 (38%)  |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         98.7%       |0.0%         0.0%         2.3%         40.2%        |
|TERMINAL (d)       |     0/25 (0%)    0/34 (0%)    0/35 (0%)    31/31 (100%)|0/38 (0%)    0/33 (0%)    0/34 (0%)    12/36 (33%)  |
|FIRST INCIDENCE    |     ---          ---          ---          351         |---          ---          651          499          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   (e)          P=0.486      P<0.001 **   |
|POLY 3             |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   (e)          P=0.485      P<0.001 **   |
|POLY 1.5           |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   (e)          P=0.489      P<0.001 **   |
|POLY 6             |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   (e)          P=0.482      P<0.001 **   |
|LOGISTIC REGRESSION|     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   (e)          P=0.537      P<0.001 **   |
|COCH-ARM / FISHERS |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   (e)          P=0.500      P<0.001 **   |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose: Olfactory Epithelium                                                                                                       |
|     Metaplasia                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/49 (0%)    47/50 (94%) |0/50 (0%)    0/50 (0%)    0/50 (0%)    47/50 (94%)  |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         97.9%       |0.0%         0.0%         0.0%         97.1%        |
|TERMINAL (d)       |     0/25 (0%)    0/34 (0%)    0/35 (0%)    31/31 (100%)|0/38 (0%)    0/33 (0%)    0/34 (0%)    36/36 (100%) |
|FIRST INCIDENCE    |     ---          ---          ---          351         |---          ---          ---          499          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   (e)          (e)          P<0.001 **   |
|POLY 3             |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   (e)          (e)          P<0.001 **   |
|POLY 1.5           |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   (e)          (e)          P<0.001 **   |
|POLY 6             |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   (e)          (e)          P<0.001 **   |
|LOGISTIC REGRESSION|     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   (e)          (e)          P<0.001 **   |
|COCH-ARM / FISHERS |     P<0.001 **   (e)          (e)          P<0.001 **  |P<0.001 **   (e)          (e)          P<0.001 **   |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 28
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary: Follicle                                                                                                                  |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |3/50 (6%)    1/50 (2%)    1/50 (2%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|                                                        |6.4%         2.3%         2.3%         2.3%         |
|TERMINAL (d)       |                                                        |3/38 (8%)    0/33 (0%)    1/34 (3%)    1/36 (3%)    |
|FIRST INCIDENCE    |                                                        |731 (T)      721          731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.343N     P=0.355N     P=0.345N     P=0.324N     |
|POLY 3             |                                                        |P=0.342N     P=0.329N     P=0.335N     P=0.326N     |
|POLY 1.5           |                                                        |P=0.343N     P=0.320N     P=0.326N     P=0.319N     |
|POLY 6             |                                                        |P=0.342N     P=0.339N     P=0.342N     P=0.332N     |
|LOGISTIC REGRESSION|                                                        |P=0.351N     P=0.352N     P=0.345N     P=0.324N     |
|COCH-ARM / FISHERS |                                                        |P=0.342N     P=0.309N     P=0.309N     P=0.309N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary: Periovarian Tissue                                                                                                        |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |4/50 (8%)    3/50 (6%)    2/50 (4%)    3/50 (6%)    |
|POLY-3 ADJUSTED (b)|                                                        |8.6%         6.8%         4.6%         6.8%         |
|TERMINAL (d)       |                                                        |3/38 (8%)    2/33 (6%)    1/34 (3%)    3/36 (8%)    |
|FIRST INCIDENCE    |                                                        |716          575          256          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.504N     P=0.573N     P=0.388N     P=0.535N     |
|POLY 3             |                                                        |P=0.514N     P=0.530N     P=0.365N     P=0.531N     |
|POLY 1.5           |                                                        |P=0.509N     P=0.519N     P=0.356N     P=0.521N     |
|POLY 6             |                                                        |P=0.518N     P=0.543N     P=0.374N     P=0.542N     |
|LOGISTIC REGRESSION|                                                        |P=0.488N     P=0.515N     P=0.247N     P=0.545N     |
|COCH-ARM / FISHERS |                                                        |P=0.500N     P=0.500N     P=0.339N     P=0.500N     |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 29
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Cytoplasmic Alteration                                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/49 (0%)    3/50 (6%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     4.9%         0.0%         6.8%         0.0%        |0.0%         0.0%         2.3%         0.0%         |
|TERMINAL (d)       |     2/25 (8%)    0/34 (0%)    3/35 (9%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    1/34 (3%)    0/36 (0%)    |
|FIRST INCIDENCE    |     729 (T)      ---          729 (T)      ---         |---          ---          731 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.272N     P=0.173N     P=0.652      P=0.192N    |P=0.782N     (e)          P=0.478      (e)          |
|POLY 3             |     P=0.307N     P=0.217N     P=0.538      P=0.225N    |P=0.790N     (e)          P=0.484      (e)          |
|POLY 1.5           |     P=0.302N     P=0.225N     P=0.522      P=0.229N    |P=0.789N     (e)          P=0.489      (e)          |
|POLY 6             |     P=0.311N     P=0.207N     P=0.562      P=0.219N    |P=0.791N     (e)          P=0.480      (e)          |
|LOGISTIC REGRESSION|     P=0.272N     (e)          P=0.652      (e)         |(e)          (e)          P=0.478      (e)          |
|COCH-ARM / FISHERS |     P=0.295N     P=0.253N     P=0.500      P=0.247N    |P=0.786N     (e)          P=0.500      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    10/49 (20%)  11/50 (22%)  12/50 (24%) |1/50 (2%)    0/50 (0%)    1/50 (2%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     9.8%         22.3%        24.6%        27.3%       |2.1%         0.0%         2.3%         2.3%         |
|TERMINAL (d)       |     4/25 (16%)   10/34 (29%)  9/35 (26%)   7/31 (23%)  |1/38 (3%)    0/33 (0%)    1/34 (3%)    1/36 (3%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      642          645         |731 (T)      ---          731 (T)      731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.096      P=0.190      P=0.150      P=0.070     |P=0.545      P=0.528N     P=0.737      P=0.750      |
|POLY 3             |     P=0.090      P=0.100      P=0.063      P=0.035 *   |P=0.540      P=0.513N     P=0.742      P=0.748      |
|POLY 1.5           |     P=0.085      P=0.088      P=0.055      P=0.031 *   |P=0.541      P=0.508N     P=0.748      P=0.752      |
|POLY 6             |     P=0.103      P=0.117      P=0.080      P=0.042 *   |P=0.539      P=0.519N     P=0.738      P=0.744      |
|LOGISTIC REGRESSION|     P=0.076      P=0.190      P=0.092      P=0.038 *   |P=0.545      (e)          P=0.737      P=0.750      |
|COCH-ARM / FISHERS |     P=0.079      P=0.068      P=0.045 *    P=0.027 *   |P=0.545      P=0.500N     P=0.753N     P=0.753N     |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 30
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas: Acinus                                                                                                                 |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     10/50 (20%)  13/49 (27%)  12/50 (24%)  14/50 (28%) |8/50 (16%)   4/50 (8%)    7/50 (14%)   10/50 (20%)  |
|POLY-3 ADJUSTED (b)|     24.1%        28.3%        25.8%        31.7%       |17.0%        9.1%         16.3%        22.4%        |
|TERMINAL (d)       |     7/25 (28%)   10/34 (29%)  9/35 (26%)   10/31 (32%) |6/38 (16%)   3/33 (9%)    6/34 (18%)   8/36 (22%)   |
|FIRST INCIDENCE    |     657          474          464          530         |589          609          711          595          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.338      P=0.583N     P=0.502N     P=0.427     |P=0.151      P=0.254N     P=0.597N     P=0.344      |
|POLY 3             |     P=0.297      P=0.420      P=0.528      P=0.295     |P=0.138      P=0.211N     P=0.576N     P=0.348      |
|POLY 1.5           |     P=0.295      P=0.378      P=0.481      P=0.277     |P=0.142      P=0.198N     P=0.552N     P=0.364      |
|POLY 6             |     P=0.304      P=0.470      P=0.588      P=0.325     |P=0.136      P=0.226N     P=0.596N     P=0.333      |
|LOGISTIC REGRESSION|     P=0.287      P=0.419      P=0.428      P=0.295     |P=0.135      P=0.192N     P=0.573N     P=0.358      |
|COCH-ARM / FISHERS |     P=0.285      P=0.298      P=0.405      P=0.241     |P=0.150      P=0.178N     P=0.500N     P=0.398      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland                                                                                                                  |
|     Angiectasis                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    0/50 (0%)    3/50 (6%)    0/50 (0%)   |6/50 (12%)   4/50 (8%)    3/50 (6%)    5/50 (10%)   |
|POLY-3 ADJUSTED (b)|     4.8%         0.0%         6.7%         0.0%        |12.8%        9.2%         6.9%         11.3%        |
|TERMINAL (d)       |     1/25 (4%)    0/34 (0%)    2/35 (6%)    0/31 (0%)   |5/38 (13%)   4/33 (12%)   2/34 (6%)    5/36 (14%)   |
|FIRST INCIDENCE    |     579          ---          722          ---         |679          731 (T)      661          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.279N     P=0.197N     P=0.622      P=0.214N    |P=0.571N     P=0.456N     P=0.300N     P=0.539N     |
|POLY 3             |     P=0.305N     P=0.219N     P=0.532      P=0.228N    |P=0.581      P=0.415N     P=0.283N     P=0.542N     |
|POLY 1.5           |     P=0.301N     P=0.225N     P=0.520      P=0.231N    |P=0.580N     P=0.397N     P=0.271N     P=0.527N     |
|POLY 6             |     P=0.309N     P=0.211N     P=0.553      P=0.224N    |P=0.577      P=0.435N     P=0.292N     P=0.557N     |
|LOGISTIC REGRESSION|     P=0.295N     P=0.252N     P=0.524      P=0.244N    |P=0.572      P=0.441N     P=0.283N     P=0.557N     |
|COCH-ARM / FISHERS |     P=0.297N     P=0.247N     P=0.500      P=0.247N    |P=0.571N     P=0.370N     P=0.243N     P=0.500N     |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 31
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland                                                                                                                  |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     5/50 (10%)   5/50 (10%)   7/50 (14%)   1/50 (2%)   |19/50 (38%)  13/50 (26%)  14/50 (28%)  15/50 (30%)  |
|POLY-3 ADJUSTED (b)|     12.0%        11.0%        15.7%        2.3%        |39.2%        29.2%        31.7%        32.5%        |
|TERMINAL (d)       |     2/25 (8%)    2/34 (6%)    5/35 (14%)   0/31 (0%)   |14/38 (37%)  10/33 (30%)  10/34 (29%)  9/36 (25%)   |
|FIRST INCIDENCE    |     617          645          712          530         |438          505          470          500          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.065N     P=0.482N     P=0.584      P=0.083N    |P=0.427N     P=0.277N     P=0.329N     P=0.352N     |
|POLY 3             |     P=0.070N     P=0.573N     P=0.425      P=0.090N    |P=0.418N     P=0.213N     P=0.298N     P=0.321N     |
|POLY 1.5           |     P=0.070N     P=0.592N     P=0.407      P=0.094N    |P=0.420N     P=0.184N     P=0.264N     P=0.303N     |
|POLY 6             |     P=0.069N     P=0.548N     P=0.453      P=0.086N    |P=0.410N     P=0.250N     P=0.327N     P=0.334N     |
|LOGISTIC REGRESSION|     P=0.072N     P=0.611N     P=0.442      P=0.109N    |P=0.426N     P=0.151N     P=0.219N     P=0.237N     |
|COCH-ARM / FISHERS |     P=0.074N     P=0.630N     P=0.380      P=0.102N    |P=0.413N     P=0.142N     P=0.198N     P=0.263N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland                                                                                                                  |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     13/50 (26%)  17/50 (34%)  16/50 (32%)  10/50 (20%) |20/50 (40%)  23/50 (46%)  16/50 (32%)  16/50 (32%)  |
|POLY-3 ADJUSTED (b)|     30.0%        36.0%        34.6%        22.8%       |41.5%        50.1%        36.3%        35.7%        |
|TERMINAL (d)       |     6/25 (24%)   12/34 (35%)  11/35 (31%)  7/31 (23%)  |16/38 (42%)  18/33 (55%)  14/34 (41%)  13/36 (36%)  |
|FIRST INCIDENCE    |     439          474          464          530         |438          441          434          549          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.115N     P=0.542      P=0.525N     P=0.194N    |P=0.145N     P=0.181      P=0.413N     P=0.344N     |
|POLY 3             |     P=0.146N     P=0.352      P=0.407      P=0.297N    |P=0.185N     P=0.262      P=0.384N     P=0.359N     |
|POLY 1.5           |     P=0.140N     P=0.318      P=0.376      P=0.302N    |P=0.168N     P=0.293      P=0.344N     P=0.326N     |
|POLY 6             |     P=0.150N     P=0.398      P=0.457      P=0.286N    |P=0.203N     P=0.227      P=0.421N     P=0.394N     |
|LOGISTIC REGRESSION|     P=0.136N     P=0.250      P=0.338      P=0.302N    |P=0.154N     P=0.329      P=0.320N     P=0.308N     |
|COCH-ARM / FISHERS |     P=0.138N     P=0.257      P=0.330      P=0.318N    |P=0.138N     P=0.343      P=0.266N     P=0.266N     |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 32
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Preputial Gland                                                                                                                  |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     26/50 (52%)  45/50 (90%)  46/50 (92%)  45/49 (92%) |                                                    |
|POLY-3 ADJUSTED (b)|     58.4%        92.7%        94.8%        93.6%       |                                                    |
|TERMINAL (d)       |     15/25 (60%)  32/34 (94%)  34/35 (97%)  28/30 (93%) |                                                    |
|FIRST INCIDENCE    |     474          474          464          351         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.033 *    P=0.061      P=0.052      P=0.018 *   |                                                    |
|POLY 3             |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |                                                    |
|POLY 1.5           |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |                                                    |
|POLY 6             |     P=0.002 **   P<0.001 **   P<0.001 **   P<0.001 **  |                                                    |
|LOGISTIC REGRESSION|     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |                                                    |
|COCH-ARM / FISHERS |     P<0.001 **   P<0.001 **   P<0.001 **   P<0.001 **  |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Prostate                                                                                                                         |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    1/50 (2%)    3/50 (6%)   |                                                    |
|POLY-3 ADJUSTED (b)|     0.0%         2.2%         2.3%         7.0%        |                                                    |
|TERMINAL (d)       |     0/25 (0%)    1/34 (3%)    1/35 (3%)    3/31 (10%)  |                                                    |
|FIRST INCIDENCE    |     ---          729 (T)      729 (T)      729 (T)     |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.067      P=0.561      P=0.567      P=0.160     |                                                    |
|POLY 3             |     P=0.066      P=0.519      P=0.516      P=0.128     |                                                    |
|POLY 1.5           |     P=0.066      P=0.513      P=0.510      P=0.125     |                                                    |
|POLY 6             |     P=0.068      P=0.528      P=0.527      P=0.133     |                                                    |
|LOGISTIC REGRESSION|     (e)          P=0.561      P=0.567      P=0.160     |                                                    |
|COCH-ARM / FISHERS |     P=0.064      P=0.500      P=0.500      P=0.121     |                                                    |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 33
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Prostate                                                                                                                         |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    5/50 (10%)   2/50 (4%)   |                                                    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         11.0%        4.6%        |                                                    |
|TERMINAL (d)       |     0/25 (0%)    0/34 (0%)    4/35 (11%)   2/31 (7%)   |                                                    |
|FIRST INCIDENCE    |     ---          ---          276          729 (T)     |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.222      (e)          P=0.062      P=0.286     |                                                    |
|POLY 3             |     P=0.208      (e)          P=0.040 *    P=0.249     |                                                    |
|POLY 1.5           |     P=0.208      (e)          P=0.036 *    P=0.245     |                                                    |
|POLY 6             |     P=0.212      (e)          P=0.046 *    P=0.255     |                                                    |
|LOGISTIC REGRESSION|     P=0.203      (e)          P=0.025 *    P=0.286     |                                                    |
|COCH-ARM / FISHERS |     P=0.208      (e)          P=0.028 *    P=0.247     |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Prostate                                                                                                                         |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     25/50 (50%)  25/50 (50%)  17/50 (34%)  24/50 (48%) |                                                    |
|POLY-3 ADJUSTED (b)|     56.2%        52.0%        36.3%        52.9%       |                                                    |
|TERMINAL (d)       |     12/25 (48%)  16/34 (47%)  11/35 (31%)  14/31 (45%) |                                                    |
|FIRST INCIDENCE    |     474          400          464          533         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.409N     P=0.205N     P=0.017N*    P=0.261N    |                                                    |
|POLY 3             |     P=0.515N     P=0.423N     P=0.042N*    P=0.458N    |                                                    |
|POLY 1.5           |     P=0.500N     P=0.468N     P=0.051N     P=0.465N    |                                                    |
|POLY 6             |     P=0.520N     P=0.378N     P=0.031N*    P=0.439N    |                                                    |
|LOGISTIC REGRESSION|     P=0.477N     P=0.533N     P=0.067N     P=0.437N    |                                                    |
|COCH-ARM / FISHERS |     P=0.484N     P=0.579N     P=0.078N     P=0.500N    |                                                    |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 34
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Seminal Vesicle                                                                                                                  |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/50 (2%)    2/50 (4%)    1/50 (2%)    4/50 (8%)   |                                                    |
|POLY-3 ADJUSTED (b)|     2.4%         4.4%         2.3%         9.2%        |                                                    |
|TERMINAL (d)       |     0/25 (0%)    2/34 (6%)    1/35 (3%)    3/31 (10%)  |                                                    |
|FIRST INCIDENCE    |     724          729 (T)      729 (T)      645         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.119      P=0.597      P=0.693N     P=0.242     |                                                    |
|POLY 3             |     P=0.113      P=0.534      P=0.742N     P=0.196     |                                                    |
|POLY 1.5           |     P=0.112      P=0.522      P=0.750N     P=0.190     |                                                    |
|POLY 6             |     P=0.115      P=0.549      P=0.730N     P=0.206     |                                                    |
|LOGISTIC REGRESSION|     P=0.109      P=0.581      P=0.707N     P=0.200     |                                                    |
|COCH-ARM / FISHERS |     P=0.108      P=0.500      P=0.753N     P=0.181     |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Hyperkeratosis                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    2/50 (4%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         4.5%         2.3%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/24 (0%)    0/34 (0%)    1/35 (3%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          ---          689          662         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.355      (e)          P=0.304      P=0.516     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.361      (e)          P=0.263      P=0.516     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.358      (e)          P=0.254      P=0.512     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.367      (e)          P=0.277      P=0.523     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.354      (e)          P=0.263      P=0.500     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.353      (e)          P=0.253      P=0.505     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 35
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    2/50 (4%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         4.5%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/24 (0%)    0/34 (0%)    1/35 (3%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          ---          689          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.692N     (e)          P=0.304      (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.693N     (e)          P=0.263      (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.693N     (e)          P=0.254      (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.690N     (e)          P=0.277      (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.694N     (e)          P=0.263      (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.695N     (e)          P=0.253      (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Fibrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     6/50 (12%)   4/50 (8%)    4/50 (8%)    4/49 (8%)   |1/50 (2%)    1/50 (2%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     14.5%        8.9%         9.0%         9.4%        |2.1%         2.3%         2.3%         0.0%         |
|TERMINAL (d)       |     4/25 (16%)   4/34 (12%)   3/35 (9%)    3/30 (10%)  |0/38 (0%)    1/33 (3%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     639          729 (T)      712          624         |690          731 (T)      651          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.380N     P=0.209N     P=0.201N     P=0.277N    |P=0.331N     P=0.731      P=0.742      P=0.514N     |
|POLY 3             |     P=0.420N     P=0.315N     P=0.323N     P=0.351N    |P=0.331N     P=0.745      P=0.743      P=0.512N     |
|POLY 1.5           |     P=0.418N     P=0.333N     P=0.341N     P=0.361N    |P=0.329N     P=0.751      P=0.748      P=0.508N     |
|POLY 6             |     P=0.420N     P=0.293N     P=0.295N     P=0.336N    |P=0.333N     P=0.738      P=0.739      P=0.516N     |
|LOGISTIC REGRESSION|     P=0.409N     P=0.271N     P=0.282N     P=0.344N    |P=0.322N     P=0.754      P=0.747N     P=0.493N     |
|COCH-ARM / FISHERS |     P=0.418N     P=0.370N     P=0.370N     P=0.383N    |P=0.323N     P=0.753N     P=0.753N     P=0.500N     |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 36
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hematopoietic Cell Proliferation                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    3/50 (6%)    3/50 (6%)    7/49 (14%)  |1/50 (2%)    8/50 (16%)   7/50 (14%)   5/50 (10%)   |
|POLY-3 ADJUSTED (b)|     9.4%         6.6%         6.6%         15.6%       |2.1%         17.0%        16.2%        10.8%        |
|TERMINAL (d)       |     1/25 (4%)    1/34 (3%)    0/35 (0%)    1/30 (3%)   |0/38 (0%)    2/33 (6%)    5/34 (15%)   1/36 (3%)    |
|FIRST INCIDENCE    |     474          641          464          456         |438          328          711          246          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.123      P=0.404N     P=0.434N     P=0.319     |P=0.429      P=0.018 *    P=0.025 *    P=0.101      |
|POLY 3             |     P=0.113      P=0.464N     P=0.460N     P=0.291     |P=0.414      P=0.015 *    P=0.021 *    P=0.096      |
|POLY 1.5           |     P=0.110      P=0.475N     P=0.476N     P=0.277     |P=0.421      P=0.016 *    P=0.024 *    P=0.098      |
|POLY 6             |     P=0.119      P=0.448N     P=0.436N     P=0.313     |P=0.410      P=0.015 *    P=0.019 *    P=0.095      |
|LOGISTIC REGRESSION|     P=0.085      P=0.574N     P=0.586N     P=0.177     |P=0.515      P=0.044 *    P=0.032 *    P=0.218      |
|COCH-ARM / FISHERS |     P=0.104      P=0.500N     P=0.500N     P=0.251     |P=0.435      P=0.015 *    P=0.030 *    P=0.102      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    3/50 (6%)    0/50 (0%)    1/50 (2%)   |1/50 (2%)    1/50 (2%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     7.3%         6.6%         0.0%         2.3%        |2.1%         2.3%         0.0%         2.3%         |
|TERMINAL (d)       |     1/25 (4%)    0/34 (0%)    0/35 (0%)    0/31 (0%)   |0/38 (0%)    1/33 (3%)    0/34 (0%)    1/36 (3%)    |
|FIRST INCIDENCE    |     701          696          ---          657         |616          731 (T)      ---          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.183N     P=0.556N     P=0.080N     P=0.259N    |P=0.671      P=0.732      P=0.522N     P=0.742      |
|POLY 3             |     P=0.192N     P=0.616N     P=0.105N     P=0.286N    |P=0.668      P=0.744      P=0.518N     P=0.746      |
|POLY 1.5           |     P=0.192N     P=0.632N     P=0.110N     P=0.292N    |P=0.671      P=0.750      P=0.512N     P=0.751      |
|POLY 6             |     P=0.192N     P=0.593N     P=0.097N     P=0.275N    |P=0.665      P=0.736      P=0.523N     P=0.741      |
|LOGISTIC REGRESSION|     P=0.191N     P=0.612N     P=0.096N     P=0.287N    |P=0.677      P=0.745N     P=0.430N     P=0.747N     |
|COCH-ARM / FISHERS |     P=0.194N     P=0.661N     P=0.121N     P=0.309N    |P=0.677      P=0.753N     P=0.500N     P=0.753N     |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 37
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    1/50 (2%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    2/50 (4%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         2.2%         0.0%         0.0%        |2.1%         4.5%         2.3%         0.0%         |
|TERMINAL (d)       |     0/25 (0%)    1/34 (3%)    0/35 (0%)    0/31 (0%)   |0/38 (0%)    1/33 (3%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     ---          729 (T)      ---          ---         |616          505          696          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.567N     P=0.561      (e)          (e)         |P=0.242N     P=0.468      P=0.737      P=0.522N     |
|POLY 3             |     P=0.563N     P=0.519      (e)          (e)         |P=0.245N     P=0.479      P=0.741      P=0.513N     |
|POLY 1.5           |     P=0.567N     P=0.513      (e)          (e)         |P=0.240N     P=0.487      P=0.747      P=0.508N     |
|POLY 6             |     P=0.557N     P=0.528      (e)          (e)         |P=0.250N     P=0.470      P=0.736      P=0.518N     |
|LOGISTIC REGRESSION|     (e)          P=0.561      (e)          (e)         |P=0.208N     P=0.615      P=0.735N     P=0.437N     |
|COCH-ARM / FISHERS |     P=0.576N     P=0.500      (e)          (e)         |P=0.231N     P=0.500      P=0.753N     P=0.500N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach                                                                                                             |
|     Ulcer                                                                                                                       |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/50 (4%)    2/50 (4%)    2/50 (4%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     4.8%         4.4%         4.5%         0.0%        |0.0%         0.0%         2.3%         0.0%         |
|TERMINAL (d)       |     0/25 (0%)    0/34 (0%)    0/35 (0%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     607          696          617          ---         |---          ---          690          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.149N     P=0.632N     P=0.626N     P=0.221N    |P=0.787N     (e)          P=0.481      (e)          |
|POLY 3             |     P=0.157N     P=0.661N     P=0.665N     P=0.228N    |P=0.790N     (e)          P=0.485      (e)          |
|POLY 1.5           |     P=0.156N     P=0.672N     P=0.677N     P=0.231N    |P=0.789N     (e)          P=0.489      (e)          |
|POLY 6             |     P=0.157N     P=0.647N     P=0.647N     P=0.224N    |P=0.791N     (e)          P=0.481      (e)          |
|LOGISTIC REGRESSION|     P=0.158N     P=0.690      P=0.685      P=0.244N    |P=0.786N     (e)          P=0.504      (e)          |
|COCH-ARM / FISHERS |     P=0.156N     P=0.691N     P=0.691N     P=0.247N    |P=0.786N     (e)          P=0.500      (e)          |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 38
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Glandular                                                                                                               |
|     Erosion                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    0/50 (0%)    5/50 (10%)   2/50 (4%)   |1/50 (2%)    1/50 (2%)    2/50 (4%)    5/50 (10%)   |
|POLY-3 ADJUSTED (b)|     7.2%         0.0%         11.2%        4.5%        |2.1%         2.3%         4.6%         11.0%        |
|TERMINAL (d)       |     0/25 (0%)    0/34 (0%)    2/35 (6%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    1/34 (3%)    1/36 (3%)    |
|FIRST INCIDENCE    |     453          ---          712          456         |514          721          711          500          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.603      P=0.100N     P=0.502      P=0.473N    |P=0.029 *    P=0.744      P=0.457      P=0.098      |
|POLY 3             |     P=0.592      P=0.106N     P=0.390      P=0.472N    |P=0.026 *    P=0.743      P=0.468      P=0.093      |
|POLY 1.5           |     P=0.590      P=0.110N     P=0.377      P=0.481N    |P=0.026 *    P=0.749      P=0.478      P=0.096      |
|POLY 6             |     P=0.596      P=0.101N     P=0.415      P=0.460N    |P=0.026 *    P=0.735      P=0.460      P=0.092      |
|LOGISTIC REGRESSION|     P=0.560      P=0.150N     P=0.361      P=0.615N    |P=0.030 *    P=0.699N     P=0.563      P=0.165      |
|COCH-ARM / FISHERS |     P=0.582      P=0.121N     P=0.357      P=0.500N    |P=0.027 *    P=0.753N     P=0.500      P=0.102      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Glandular                                                                                                               |
|     Ulcer                                                                                                                       |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/50 (8%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     9.6%         0.0%         0.0%         0.0%        |2.1%         0.0%         0.0%         2.2%         |
|TERMINAL (d)       |     0/25 (0%)    0/34 (0%)    0/35 (0%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     617          ---          ---          ---         |616          ---          ---          595          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.072N     P=0.046N*    P=0.044N*    P=0.053N    |P=0.522      P=0.522N     P=0.522N     P=0.738      |
|POLY 3             |     P=0.081N     P=0.050N     P=0.052N     P=0.055N    |P=0.539      P=0.515N     P=0.518N     P=0.748      |
|POLY 1.5           |     P=0.078N     P=0.054N     P=0.055N     P=0.057N    |P=0.538      P=0.509N     P=0.512N     P=0.752      |
|POLY 6             |     P=0.085N     P=0.047N*    P=0.048N*    P=0.054N    |P=0.542      P=0.522N     P=0.523N     P=0.745      |
|LOGISTIC REGRESSION|     P=0.077N     P=0.060N     P=0.060N     P=0.061N    |P=0.569      P=0.432N     P=0.430N     P=0.696N     |
|COCH-ARM / FISHERS |     P=0.077N     P=0.059N     P=0.059N     P=0.059N    |P=0.536      P=0.500N     P=0.500N     P=0.753N     |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 39
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     6/50 (12%)   6/50 (12%)   5/50 (10%)   2/50 (4%)   |                                                    |
|POLY-3 ADJUSTED (b)|     14.4%        13.2%        11.0%        4.6%        |                                                    |
|TERMINAL (d)       |     2/25 (8%)    4/34 (12%)   3/35 (9%)    2/31 (7%)   |                                                    |
|FIRST INCIDENCE    |     617          697          464          729 (T)     |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.075N     P=0.444N     P=0.339N     P=0.093N    |                                                    |
|POLY 3             |     P=0.086N     P=0.559N     P=0.438N     P=0.120N    |                                                    |
|POLY 1.5           |     P=0.085N     P=0.579N     P=0.462N     P=0.124N    |                                                    |
|POLY 6             |     P=0.086N     P=0.534N     P=0.405N     P=0.115N    |                                                    |
|LOGISTIC REGRESSION|     P=0.083N     P=0.545N     P=0.493N     P=0.115N    |                                                    |
|COCH-ARM / FISHERS |     P=0.086N     P=0.620N     P=0.500N     P=0.134N    |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes: Interstitial Cell                                                                                                        |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     9/50 (18%)   6/50 (12%)   4/50 (8%)    3/50 (6%)   |                                                    |
|POLY-3 ADJUSTED (b)|     20.2%        13.2%        8.8%         6.7%        |                                                    |
|TERMINAL (d)       |     1/25 (4%)    3/34 (9%)    2/35 (6%)    0/31 (0%)   |                                                    |
|FIRST INCIDENCE    |     453          697          464          351         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.067N     P=0.191N     P=0.084N     P=0.061N    |                                                    |
|POLY 3             |     P=0.063N     P=0.273N     P=0.106N     P=0.056N    |                                                    |
|POLY 1.5           |     P=0.062N     P=0.275N     P=0.110N     P=0.056N    |                                                    |
|POLY 6             |     P=0.063N     P=0.266N     P=0.098N     P=0.055N    |                                                    |
|LOGISTIC REGRESSION|     P=0.071N     P=0.383N     P=0.163N     P=0.089N    |                                                    |
|COCH-ARM / FISHERS |     P=0.065N     P=0.288N     P=0.117N     P=0.061N    |                                                    |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 40
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: C-Cell                                                                                                            |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     23/50 (46%)  29/50 (58%)  35/50 (70%)  29/50 (58%) |36/50 (72%)  25/50 (50%)  37/50 (74%)  32/50 (64%)  |
|POLY-3 ADJUSTED (b)|     54.5%        62.2%        74.8%        66.1%       |76.0%        56.1%        82.9%        70.3%        |
|TERMINAL (d)       |     15/25 (60%)  22/34 (65%)  28/35 (80%)  24/31 (77%) |35/38 (92%)  20/33 (61%)  31/34 (91%)  29/36 (81%)  |
|FIRST INCIDENCE    |     617          592          464          624         |438          609          470          499          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.408      P=0.496N     P=0.314      P=0.495     |P=0.519      P=0.087N     P=0.130      P=0.366N     |
|POLY 3             |     P=0.233      P=0.296      P=0.030 *    P=0.178     |P=0.476      P=0.029N*    P=0.273      P=0.345N     |
|POLY 1.5           |     P=0.256      P=0.241      P=0.020 *    P=0.176     |P=0.484      P=0.025N*    P=0.332      P=0.320N     |
|POLY 6             |     P=0.209      P=0.378      P=0.053      P=0.187     |P=0.470      P=0.030N*    P=0.255      P=0.358N     |
|LOGISTIC REGRESSION|     P=0.272      P=0.367      P=0.030 *    P=0.265     |P=0.396      P=0.052N     P=0.196      P=0.428N     |
|COCH-ARM / FISHERS |     P=0.270      P=0.158      P=0.013 *    P=0.158     |P=0.513      P=0.020N*    P=0.500      P=0.260N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicular Cell                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/50 (6%)    0/50 (0%)    0/50 (0%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     7.1%         0.0%         0.0%         2.3%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/25 (4%)    0/34 (0%)    0/35 (0%)    0/31 (0%)   |0/38 (0%)    0/33 (0%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |     493          ---          ---          645         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.442N     P=0.099N     P=0.103N     P=0.277N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.465N     P=0.107N     P=0.109N     P=0.294N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.459N     P=0.110N     P=0.113N     P=0.297N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.473N     P=0.102N     P=0.103N     P=0.287N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.477N     P=0.157N     P=0.143N     P=0.347N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.448N     P=0.121N     P=0.121N     P=0.309N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 41
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Hydrometra                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |2/50 (4%)    2/50 (4%)    2/50 (4%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|                                                        |4.3%         4.5%         4.6%         4.5%         |
|TERMINAL (d)       |                                                        |2/38 (5%)    1/33 (3%)    1/34 (3%)    1/36 (3%)    |
|FIRST INCIDENCE    |                                                        |731 (T)      609          256          589          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.613      P=0.647      P=0.663      P=0.671      |
|POLY 3             |                                                        |P=0.610      P=0.673      P=0.673      P=0.678      |
|POLY 1.5           |                                                        |P=0.612      P=0.681      P=0.680      P=0.682      |
|POLY 6             |                                                        |P=0.608      P=0.666      P=0.666      P=0.673      |
|LOGISTIC REGRESSION|                                                        |P=0.588N     P=0.695      P=0.571N     P=0.691N     |
|COCH-ARM / FISHERS |                                                        |P=0.621      P=0.691N     P=0.691N     P=0.691N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |0/50 (0%)    2/50 (4%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|                                                        |0.0%         4.6%         0.0%         0.0%         |
|TERMINAL (d)       |                                                        |0/38 (0%)    2/33 (6%)    0/34 (0%)    0/36 (0%)    |
|FIRST INCIDENCE    |                                                        |---          731 (T)      ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.370N     P=0.208      (e)          (e)          |
|POLY 3             |                                                        |P=0.385N     P=0.223      (e)          (e)          |
|POLY 1.5           |                                                        |P=0.379N     P=0.228      (e)          (e)          |
|POLY 6             |                                                        |P=0.392N     P=0.217      (e)          (e)          |
|LOGISTIC REGRESSION|                                                        |(e)          P=0.208      (e)          (e)          |
|COCH-ARM / FISHERS |                                                        |P=0.369N     P=0.247      (e)          (e)          |
|=================================================================================================================================|
       Date:  02/24/00                           EXPERIMENT: 88050 TEST: 05                                            Page 42
                     Statistical Analysis of Non-neoplastic Lesions in       Rats(FISCHER 344)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus: Cervix                                                                                                                   |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |0/50 (0%)    0/50 (0%)    3/50 (6%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|                                                        |0.0%         0.0%         7.0%         2.3%         |
|TERMINAL (d)       |                                                        |0/38 (0%)    0/33 (0%)    2/34 (6%)    1/36 (3%)    |
|FIRST INCIDENCE    |                                                        |---          ---          711          731 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.379      (e)          P=0.102      P=0.489      |
|POLY 3             |                                                        |P=0.364      (e)          P=0.105      P=0.489      |
|POLY 1.5           |                                                        |P=0.369      (e)          P=0.109      P=0.493      |
|POLY 6             |                                                        |P=0.359      (e)          P=0.102      P=0.485      |
|LOGISTIC REGRESSION|                                                        |P=0.371      (e)          P=0.102      P=0.489      |
|COCH-ARM / FISHERS |                                                        |P=0.381      (e)          P=0.121      P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG    |0 MG/KG      3 MG/KG      10 MG/KG     30 MG/KG     |
|                   |                                                        |                                                    |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus: Endometrium                                                                                                              |
|     Hyperplasia Cystic                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |4/50 (8%)    1/50 (2%)    3/50 (6%)    3/50 (6%)    |
|POLY-3 ADJUSTED (b)|                                                        |8.5%         2.3%         6.9%         6.8%         |
|TERMINAL (d)       |                                                        |2/38 (5%)    1/33 (3%)    1/34 (3%)    2/36 (6%)    |
|FIRST INCIDENCE    |                                                        |679          731 (T)      661          730          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.550      P=0.225N     P=0.559N     P=0.532N     |
|POLY 3             |                                                        |P=0.547      P=0.201N     P=0.542N     P=0.533N     |
|POLY 1.5           |                                                        |P=0.549      P=0.193N     P=0.530N     P=0.522N     |
|POLY 6             |                                                        |P=0.545      P=0.212N     P=0.551N     P=0.546N     |
|LOGISTIC REGRESSION|                                                        |P=0.540      P=0.201N     P=0.524N     P=0.538N     |
|COCH-ARM / FISHERS |                                                        |P=0.555      P=0.181N     P=0.500N     P=0.500N     |
|=================================================================================================================================|

(a)  Number of tumor-bearing animals /  number of animals examined at site.
(b)  Poly-3 adjusted lifetime tumor incidence.
(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.
(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).