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TDMS Study 88050-06 Pathology Tables

NTP                                    STATISTICAL ANALYSIS OF NON-NEOPLASTIC LESIONS                          REPORT: PEIRPT10     
LAB: Battelle Columbus                                     METHACRYLONITRILE                                   DATE: 10/25/99       
EXPERIMENT: 88050 TEST: 06                                                                                     TIME: 08:33:40       
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                   PAGE:       1        
CONT: NO1-ES-55388                              ROUTE: GAVAGE                                                  NTP C#: 88050B       
PATHOLOGIST: TOFT, JOHN                                                                                        CAS: 126-98-7        
------------------------------------------------------------------------------------------------------------------------------------
                                                      FINAL#1, CORE STUDY MICE                                                      
               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: 10/25/99     
EXPERIMENT: 88050 TEST: 06                                                                                     TIME: 08:33:40     
TEST TYPE:  CHRONIC                             CAGES FROM 0000 TO LAST CAGE                                                      
CONT: NO1-ES-55388                              ROUTE: GAVAGE                                                  NTP C#: 88050B     
PATHOLOGIST: TOFT, JOHN                                                                                        CAS: 126-98-7      
SUMMARY OF STATISTICALLY SIGNIFICANT (P<=.05) RESULTS
IN THE ANALYSIS OF                METHACRYLONITRILE
===============================================================
Male Mice
------------
Organ                                 Morphology
-----                                 ----------
Adrenal Cortex                         Hypertrophy
Adrenal Cortex: Capsule                Hyperplasia
Epididymis                             Infiltration Cellular Mononuclear Cell
Islets, Pancreatic                     Hyperplasia
Kidney                                 Infiltration Cellular Mononuclear Cell
                                       Mineralization
                                       Nephropathy
Kidney: Renal Tubule                   Hyperplasia
Liver                                  Basophilic Focus
                                       Eosinophilic Focus
                                       Mixed Cell Focus
                                       Necrosis
Liver: Hepatocyte                      Vacuolization Cytoplasmic
Nose: Nasolacrimal Duct                Inflammation
Oral Mucosa: Gingival                  Inflammation Acute
                                       Inflammation Chronic
Preputial Gland                        Infiltration Cellular Mononuclear Cell
                                       Inflammation Chronic
Prostate                               Infiltration Cellular Mononuclear Cell
Salivary Glands                        Infiltration Cellular Mononuclear Cell
Spleen                                 Hematopoietic Cell Proliferation
Stomach, Glandular: Glands             Ectasia
===============================================================
Female Mice
------------
Organ                                  Morphology
-----                                  ----------
Adrenal Cortex                         Accessory Adrenal Cortical Nodule
Adrenal Cortex: Capsule                Hyperplasia
Clitoral Gland: Duct                   Cyst
Intestine Small, Jejunum: Peyer's Patch
                                       Hyperplasia Lymphoid
Kidney                                 Accumulation, Hyaline Droplet
                                       Infiltration Cellular Mononuclear Cell
Liver                                  Basophilic Focus
                                       Infiltration Cellular Mononuclear Cell
                                       Inflammation Chronic
                                       Pigmentation
Liver: Hepatocyte                      Vacuolization Cytoplasmic
Lymph Node, Mandibular                 Pigmentation
Mammary Gland                          Hyperplasia Cystic
Mesentery                              Mineralization
Ovary                                  Pigmentation
Pancreas                               Infiltration Cellular Mononuclear Cell
Spleen                                 Hematopoietic Cell Proliferation
Stomach, Glandular: Glands             Ectasia
Uterus: Endometrium                    Hyperplasia Cystic
===============================================================
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 1
                     Statistical Analysis of Non-neoplastic Lesions in        Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Accessory Adrenal Cortical Nodule                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         0.0%         5.7%         |
|TERMINAL (d)       |     0/35 (0%)    0/43 (0%)    0/43 (0%)    0/22 (0%)   |0/34 (0%)    0/35 (0%)    0/43 (0%)    2/25 (8%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          ---          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.024 *    (e)          (e)          P=0.173      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.040 *    (e)          (e)          P=0.189      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.041 *    (e)          (e)          P=0.206      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.040 *    (e)          (e)          P=0.176      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          P=0.173      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.047 *    (e)          (e)          P=0.253      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     14/49 (29%)  12/50 (24%)  16/50 (32%)  7/50 (14%)  |0/49 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     30.9%        25.0%        33.3%        22.0%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     13/35 (37%)  11/43 (26%)  14/43 (33%)  6/22 (27%)  |0/34 (0%)    0/35 (0%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     600          629          429          481         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.417N     P=0.209N     P=0.516N     P=0.358N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.362N     P=0.346N     P=0.488      P=0.279N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.233N     P=0.364N     P=0.464      P=0.170N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.477N     P=0.320N     P=0.530      P=0.402N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.351N     P=0.325N     P=0.447      P=0.394N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.071N     P=0.387N     P=0.440      P=0.063N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 2
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex                                                                                                                   |
|     Hypertrophy                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     26/49 (53%)  34/50 (68%)  28/50 (56%)  15/50 (30%) |1/49 (2%)    0/50 (0%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     56.0%        70.9%        59.7%        44.2%       |2.2%         0.0%         2.1%         0.0%         |
|TERMINAL (d)       |     21/35 (60%)  32/43 (74%)  27/43 (63%)  11/22 (50%) |0/34 (0%)    0/35 (0%)    1/43 (2%)    0/25 (0%)    |
|FIRST INCIDENCE    |     501          644          703          481         |625          ---          730 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.253N     P=0.396      P=0.331N     P=0.396N    |P=0.462N     P=0.514N     P=0.732N     P=0.574N     |
|POLY 3             |     P=0.120N     P=0.092      P=0.441      P=0.204N    |P=0.426N     P=0.507N     P=0.746N     P=0.548N     |
|POLY 1.5           |     P=0.034N*    P=0.092      P=0.442      P=0.088N    |P=0.419N     P=0.504N     P=0.750N     P=0.530N     |
|POLY 6             |     P=0.262N     P=0.095      P=0.463      P=0.373N    |P=0.431N     P=0.507N     P=0.740N     P=0.563N     |
|LOGISTIC REGRESSION|     P=0.236N     P=0.143      P=0.530      P=0.257N    |P=0.397N     P=0.457N     P=0.741      P=0.453N     |
|COCH-ARM / FISHERS |     P=0.002N**   P=0.094      P=0.463      P=0.017N*   |P=0.402N     P=0.495N     P=0.747N     P=0.495N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Adrenal Cortex: Capsule                                                                                                          |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     41/49 (84%)  41/50 (82%)  40/50 (80%)  45/50 (90%) |48/49 (98%)  48/50 (96%)  50/50 (100%) 50/50 (100%) |
|POLY-3 ADJUSTED (b)|     83.8%        82.5%        81.5%        96.8%       |98.0%        99.3%        100.0%       100.0%       |
|TERMINAL (d)       |     28/35 (80%)  35/43 (81%)  35/43 (81%)  22/22 (100%)|34/34 (100%) 35/35 (100%) 43/43 (100%) 25/25 (100%) |
|FIRST INCIDENCE    |     501          563          429          481         |362          374          533          212          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.136N     P=0.101N     P<0.001 **  |P=0.003 **   P=0.540N     P=0.072N     P=0.010 *    |
|POLY 3             |     P=0.033 *    P=0.538N     P=0.486N     P=0.029 *   |P=0.254      P=0.637      P=0.501      P=0.501      |
|POLY 1.5           |     P=0.060      P=0.529N     P=0.462N     P=0.064     |P=0.216      P=0.752      P=0.498      P=0.498      |
|POLY 6             |     P=0.018 *    P=0.551N     P=0.505N     P=0.012 *   |P=0.292      P=0.547      P=0.506      P=0.506      |
|LOGISTIC REGRESSION|     P=0.097      P=0.583N     P=0.420N     P=0.084     |P=0.052      P=0.744N     P=0.468      P=0.565      |
|COCH-ARM / FISHERS |     P=0.206      P=0.518N     P=0.416N     P=0.264     |P=0.185      P=0.508N     P=0.495      P=0.495      |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 3
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone Marrow                                                                                                                      |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    4/50 (8%)    0/50 (0%)   |2/50 (4%)    2/50 (4%)    4/50 (8%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         8.3%         0.0%        |4.4%         4.7%         8.2%         2.8%         |
|TERMINAL (d)       |     0/35 (0%)    0/43 (0%)    2/43 (5%)    0/22 (0%)   |1/35 (3%)    2/35 (6%)    1/43 (2%)    0/25 (0%)    |
|FIRST INCIDENCE    |     ---          ---          439          ---         |607          730 (T)      589          641          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.385      (e)          P=0.080      (e)         |P=0.577N     P=0.683      P=0.374      P=0.626N     |
|POLY 3             |     P=0.205      (e)          P=0.070      (e)         |P=0.558N     P=0.673      P=0.371      P=0.589N     |
|POLY 1.5           |     P=0.310      (e)          P=0.067      (e)         |P=0.516N     P=0.678      P=0.357      P=0.558N     |
|POLY 6             |     P=0.139      (e)          P=0.076      (e)         |P=0.549      P=0.673      P=0.390      P=0.612N     |
|LOGISTIC REGRESSION|     P=0.529N     (e)          P=0.077      (e)         |P=0.375N     P=0.688      P=0.193      P=0.500N     |
|COCH-ARM / FISHERS |     P=0.505      (e)          P=0.061      (e)         |P=0.431N     P=0.691N     P=0.339      P=0.500N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Bone Marrow                                                                                                                      |
|     Myelofibrosis                                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |2/50 (4%)    3/50 (6%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |4.4%         7.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/35 (0%)    0/43 (0%)    0/43 (0%)    0/22 (0%)   |1/35 (3%)    3/35 (9%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |727          730 (T)      ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.092N     P=0.497      P=0.199N     P=0.320N     |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.084N     P=0.478      P=0.226N     P=0.299N     |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.081N     P=0.483      P=0.230N     P=0.276N     |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.084N     P=0.480      P=0.219N     P=0.319N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.092N     P=0.504      P=0.203N     P=0.316N     |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.073N     P=0.500      P=0.247N     P=0.247N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 4
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Brain                                                                                                                            |
|     Infiltration Cellular Mononuclear Cell                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |2/50 (4%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |4.4%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/35 (0%)    0/43 (0%)    0/43 (0%)    0/22 (0%)   |2/35 (6%)    0/35 (0%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |730 (T)      ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.124N     P=0.238N     P=0.194N     P=0.315N     |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.094N     P=0.248N     P=0.226N     P=0.299N     |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.102N     P=0.246N     P=0.230N     P=0.276N     |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.086N     P=0.247N     P=0.219N     P=0.319N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.124N     (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.115N     P=0.247N     P=0.247N     P=0.247N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral Gland                                                                                                                   |
|     Infiltration Cellular Mononuclear Cell                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |4/50 (8%)    2/50 (4%)    3/50 (6%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|                                                        |8.8%         4.7%         6.3%         2.9%         |
|TERMINAL (d)       |                                                        |3/35 (9%)    2/35 (6%)    1/43 (2%)    1/25 (4%)    |
|FIRST INCIDENCE    |                                                        |593          730 (T)      653          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.246N     P=0.348N     P=0.421N     P=0.302N     |
|POLY 3             |                                                        |P=0.232N     P=0.364N     P=0.473N     P=0.282N     |
|POLY 1.5           |                                                        |P=0.210N     P=0.357N     P=0.484N     P=0.244N     |
|POLY 6             |                                                        |P=0.247N     P=0.365N     P=0.456N     P=0.314N     |
|LOGISTIC REGRESSION|                                                        |P=0.218N     P=0.353N     P=0.532N     P=0.269N     |
|COCH-ARM / FISHERS |                                                        |P=0.167N     P=0.339N     P=0.500N     P=0.187N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 5
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral Gland                                                                                                                   |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |2/50 (4%)    1/50 (2%)    0/50 (0%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|                                                        |4.4%         2.3%         0.0%         2.9%         |
|TERMINAL (d)       |                                                        |2/35 (6%)    1/35 (3%)    0/43 (0%)    1/25 (4%)    |
|FIRST INCIDENCE    |                                                        |730 (T)      730 (T)      ---          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.440N     P=0.500N     P=0.194N     P=0.617N     |
|POLY 3             |                                                        |P=0.359N     P=0.517N     P=0.226N     P=0.597N     |
|POLY 1.5           |                                                        |P=0.368N     P=0.513N     P=0.230N     P=0.566N     |
|POLY 6             |                                                        |P=0.345N     P=0.515N     P=0.219N     P=0.622N     |
|LOGISTIC REGRESSION|                                                        |P=0.440N     P=0.500N     (e)          P=0.617N     |
|COCH-ARM / FISHERS |                                                        |P=0.372N     P=0.500N     P=0.247N     P=0.508N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Clitoral Gland: Duct                                                                                                             |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |0/50 (0%)    0/50 (0%)    2/50 (4%)    2/49 (4%)    |
|POLY-3 ADJUSTED (b)|                                                        |0.0%         0.0%         4.2%         5.9%         |
|TERMINAL (d)       |                                                        |0/35 (0%)    0/35 (0%)    2/43 (5%)    2/25 (8%)    |
|FIRST INCIDENCE    |                                                        |---          ---          730 (T)      730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.043 *    (e)          P=0.285      P=0.167      |
|POLY 3             |                                                        |P=0.048 *    (e)          P=0.249      P=0.180      |
|POLY 1.5           |                                                        |P=0.058      (e)          P=0.244      P=0.197      |
|POLY 6             |                                                        |P=0.041 *    (e)          P=0.256      P=0.167      |
|LOGISTIC REGRESSION|                                                        |(e)          (e)          P=0.285      P=0.167      |
|COCH-ARM / FISHERS |                                                        |P=0.083      (e)          P=0.247      P=0.242      |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 6
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Epididymis                                                                                                                       |
|     Granuloma Sperm                                                                                                             |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/49 (4%)    0/50 (0%)    1/50 (2%)    0/50 (0%)   |                                                    |
|POLY-3 ADJUSTED (b)|     4.4%         0.0%         2.1%         0.0%        |                                                    |
|TERMINAL (d)       |     1/35 (3%)    0/43 (0%)    1/43 (2%)    0/22 (0%)   |                                                    |
|FIRST INCIDENCE    |     663          ---          729 (T)      ---         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.252N     P=0.215N     P=0.447N     P=0.365N    |                                                    |
|POLY 3             |     P=0.212N     P=0.226N     P=0.487N     P=0.329N    |                                                    |
|POLY 1.5           |     P=0.206N     P=0.229N     P=0.491N     P=0.291N    |                                                    |
|POLY 6             |     P=0.226N     P=0.222N     P=0.479N     P=0.366N    |                                                    |
|LOGISTIC REGRESSION|     P=0.223N     P=0.246N     P=0.493N     P=0.313N    |                                                    |
|COCH-ARM / FISHERS |     P=0.185N     P=0.242N     P=0.492N     P=0.242N    |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Epididymis                                                                                                                       |
|     Infiltration Cellular Mononuclear Cell                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     15/49 (31%)  26/50 (52%)  30/50 (60%)  21/50 (42%) |                                                    |
|POLY-3 ADJUSTED (b)|     32.7%        54.6%        62.8%        57.0%       |                                                    |
|TERMINAL (d)       |     10/35 (29%)  25/43 (58%)  28/43 (65%)  12/22 (55%) |                                                    |
|FIRST INCIDENCE    |     600          714          502          481         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.002 **   P=0.115      P=0.028 *    P=0.012 *   |                                                    |
|POLY 3             |     P=0.014 *    P=0.024 *    P=0.002 **   P=0.020 *   |                                                    |
|POLY 1.5           |     P=0.044 *    P=0.024 *    P=0.002 **   P=0.048 *   |                                                    |
|POLY 6             |     P=0.004 **   P=0.024 *    P=0.003 **   P=0.008 **  |                                                    |
|LOGISTIC REGRESSION|     P=0.013 *    P=0.040 *    P=0.003 **   P=0.046 *   |                                                    |
|COCH-ARM / FISHERS |     P=0.244      P=0.025 *    P=0.003 **   P=0.166     |                                                    |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 7
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Epididymis                                                                                                                       |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/49 (4%)    0/50 (0%)    1/50 (2%)    0/50 (0%)   |                                                    |
|POLY-3 ADJUSTED (b)|     4.4%         0.0%         2.1%         0.0%        |                                                    |
|TERMINAL (d)       |     1/35 (3%)    0/43 (0%)    1/43 (2%)    0/22 (0%)   |                                                    |
|FIRST INCIDENCE    |     650          ---          729 (T)      ---         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.253N     P=0.217N     P=0.447N     P=0.368N    |                                                    |
|POLY 3             |     P=0.212N     P=0.226N     P=0.488N     P=0.329N    |                                                    |
|POLY 1.5           |     P=0.206N     P=0.229N     P=0.491N     P=0.291N    |                                                    |
|POLY 6             |     P=0.226N     P=0.222N     P=0.479N     P=0.367N    |                                                    |
|LOGISTIC REGRESSION|     P=0.212N     P=0.252N     P=0.494N     P=0.298N    |                                                    |
|COCH-ARM / FISHERS |     P=0.185N     P=0.242N     P=0.492N     P=0.242N    |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart                                                                                                                            |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/48 (4%)    1/50 (2%)    0/50 (0%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     4.5%         2.1%         0.0%         3.2%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/35 (3%)    1/43 (2%)    0/43 (0%)    1/22 (5%)   |0/35 (0%)    0/35 (0%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     650          729 (T)      ---          729 (T)     |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.499N     P=0.452N     P=0.213N     P=0.678N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.347N     P=0.475N     P=0.225N     P=0.618N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.361N     P=0.479N     P=0.227N     P=0.570N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.336N     P=0.469N     P=0.220N     P=0.661N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.456N     P=0.498N     P=0.228N     P=0.642N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.357N     P=0.485N     P=0.237N     P=0.485N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 8
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Heart                                                                                                                            |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/48 (4%)    0/50 (0%)    1/50 (2%)    1/50 (2%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     4.5%         0.0%         2.1%         3.2%        |2.2%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/35 (0%)    0/43 (0%)    1/43 (2%)    1/22 (5%)   |0/35 (0%)    0/35 (0%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     650          ---          729 (T)      729 (T)     |623          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.647      P=0.229N     P=0.458N     P=0.687N    |P=0.343N     P=0.518N     P=0.500N     P=0.579N     |
|POLY 3             |     P=0.517N     P=0.222N     P=0.481N     P=0.619N    |P=0.258N     P=0.511N     P=0.491N     P=0.553N     |
|POLY 1.5           |     P=0.517N     P=0.225N     P=0.485N     P=0.570N    |P=0.278N     P=0.508N     P=0.495N     P=0.534N     |
|POLY 6             |     P=0.523N     P=0.219N     P=0.474N     P=0.662N    |P=0.240N     P=0.511N     P=0.486N     P=0.568N     |
|LOGISTIC REGRESSION|     P=0.574N     P=0.268N     P=0.486N     P=0.613N    |P=0.257N     P=0.459N     P=0.591N     P=0.453N     |
|COCH-ARM / FISHERS |     P=0.490N     P=0.237N     P=0.485N     P=0.485N    |P=0.306N     P=0.500N     P=0.500N     P=0.500N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small, Duodenum                                                                                                        |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    3/49 (6%)    1/50 (2%)    1/50 (2%)   |0/49 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         6.4%         2.1%         3.2%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/35 (0%)    3/43 (7%)    1/43 (2%)    1/22 (5%)   |0/35 (0%)    0/35 (0%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     ---          729 (T)      729 (T)      729 (T)     |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.442      P=0.160      P=0.541      P=0.407     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.422      P=0.127      P=0.508      P=0.429     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.485      P=0.123      P=0.506      P=0.456     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.388      P=0.132      P=0.514      P=0.405     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          P=0.160      P=0.541      P=0.407     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.598      P=0.121      P=0.505      P=0.505     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 9
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Intestine Small, Jejunum: Peyer's Patch                                                                                          |
|     Hyperplasia Lymphoid                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    1/50 (2%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         2.1%         3.2%        |0.0%         0.0%         0.0%         5.6%         |
|TERMINAL (d)       |     0/35 (0%)    0/43 (0%)    1/43 (2%)    1/22 (5%)   |0/35 (0%)    0/35 (0%)    0/43 (0%)    1/25 (4%)    |
|FIRST INCIDENCE    |     ---          ---          729 (T)      729 (T)     |---          ---          ---          480          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.140      (e)          P=0.541      P=0.407     |P=0.034 *    (e)          (e)          P=0.199      |
|POLY 3             |     P=0.142      (e)          P=0.508      P=0.429     |P=0.040 *    (e)          (e)          P=0.188      |
|POLY 1.5           |     P=0.174      (e)          P=0.506      P=0.456     |P=0.041 *    (e)          (e)          P=0.204      |
|POLY 6             |     P=0.129      (e)          P=0.514      P=0.405     |P=0.040 *    (e)          (e)          P=0.177      |
|LOGISTIC REGRESSION|     (e)          (e)          P=0.541      P=0.407     |P=0.076      (e)          (e)          P=0.292      |
|COCH-ARM / FISHERS |     P=0.238      (e)          P=0.505      P=0.505     |P=0.046 *    (e)          (e)          P=0.247      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Islets, Pancreatic                                                                                                               |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     47/49 (96%)  43/50 (86%)  48/50 (96%)  46/50 (92%) |41/50 (82%)  37/50 (74%)  40/50 (80%)  33/49 (67%)  |
|POLY-3 ADJUSTED (b)|     96.6%        86.1%        96.0%        96.7%       |85.2%        80.8%        81.5%        73.8%        |
|TERMINAL (d)       |     35/35 (100%) 37/43 (86%)  41/43 (95%)  21/22 (96%) |31/35 (89%)  29/35 (83%)  37/43 (86%)  15/25 (60%)  |
|FIRST INCIDENCE    |     501          563          429          481         |492          405          533          212          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.012N*    P=0.081N     P=0.004 **  |P=0.327      P=0.302N     P=0.057N     P=0.394      |
|POLY 3             |     P=0.276      P=0.062N     P=0.648N     P=0.730     |P=0.106N     P=0.382N     P=0.411N     P=0.126N     |
|POLY 1.5           |     P=0.336      P=0.072N     P=0.675N     P=0.654N    |P=0.097N     P=0.332N     P=0.438N     P=0.106N     |
|POLY 6             |     P=0.245      P=0.047N*    P=0.594N     P=0.729     |P=0.105N     P=0.407N     P=0.390N     P=0.133N     |
|LOGISTIC REGRESSION|     P=0.345      P=0.094N     P=0.688      P=0.588     |P=0.233N     P=0.381N     P=0.390N     P=0.122N     |
|COCH-ARM / FISHERS |     P=0.528N     P=0.085N     P=0.684      P=0.349N    |P=0.079N     P=0.235N     P=0.500N     P=0.074N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 10
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Accumulation, Hyaline Droplet                                                                                               |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |2/50 (4%)    1/50 (2%)    0/49 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |4.4%         2.3%         0.0%         0.0%         |
|TERMINAL (d)       |     0/35 (0%)    0/43 (0%)    0/43 (0%)    0/22 (0%)   |0/35 (0%)    0/35 (0%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |623          422          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.120N     P=0.524N     P=0.232N     P=0.330N     |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.098N     P=0.515N     P=0.231N     P=0.303N     |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.101N     P=0.511N     P=0.236N     P=0.278N     |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.093N     P=0.516N     P=0.226N     P=0.325N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.040N*    P=0.355N     P=0.317N     P=0.191N     |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.101N     P=0.500N     P=0.253N     P=0.247N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Infarct                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/49 (4%)    2/50 (4%)    1/50 (2%)    0/50 (0%)   |1/50 (2%)    0/50 (0%)    0/49 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     4.5%         4.2%         2.1%         0.0%        |2.2%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     2/35 (6%)    2/43 (5%)    1/43 (2%)    0/22 (0%)   |0/35 (0%)    0/35 (0%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      ---         |593          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.181N     P=0.619N     P=0.428N     P=0.345N    |P=0.348N     P=0.527N     P=0.508N     P=0.587N     |
|POLY 3             |     P=0.173N     P=0.673N     P=0.485N     P=0.328N    |P=0.258N     P=0.512N     P=0.494N     P=0.553N     |
|POLY 1.5           |     P=0.157N     P=0.679N     P=0.490N     P=0.290N    |P=0.278N     P=0.509N     P=0.498N     P=0.534N     |
|POLY 6             |     P=0.192N     P=0.664N     P=0.475N     P=0.364N    |P=0.239N     P=0.512N     P=0.488N     P=0.568N     |
|LOGISTIC REGRESSION|     P=0.181N     P=0.619N     P=0.428N     (e)         |P=0.237N     P=0.437N     P=0.643N     P=0.415N     |
|COCH-ARM / FISHERS |     P=0.122N     P=0.684N     P=0.492N     P=0.242N    |P=0.306N     P=0.500N     P=0.505N     P=0.500N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 11
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Infiltration Cellular Mononuclear Cell                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     26/49 (53%)  37/50 (74%)  39/50 (78%)  22/50 (44%) |35/50 (70%)  42/50 (84%)  44/49 (90%)  35/50 (70%)  |
|POLY-3 ADJUSTED (b)|     57.3%        77.3%        82.8%        58.7%       |75.9%        89.5%        92.5%        81.8%        |
|TERMINAL (d)       |     23/35 (66%)  36/43 (84%)  38/43 (88%)  13/22 (59%) |31/35 (89%)  32/35 (91%)  42/43 (98%)  23/25 (92%)  |
|FIRST INCIDENCE    |     650          644          655          481         |607          374          589          480          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.075      P=0.188      P=0.091      P=0.205     |P=0.018 *    P=0.083      P=0.465      P=0.020 *    |
|POLY 3             |     P=0.468      P=0.026 *    P=0.004 **   P=0.538     |P=0.316      P=0.057      P=0.017 *    P=0.323      |
|POLY 1.5           |     P=0.375N     P=0.025 *    P=0.004 **   P=0.491N    |P=0.426      P=0.054      P=0.014 *    P=0.401      |
|POLY 6             |     P=0.287      P=0.030 *    P=0.005 **   P=0.411     |P=0.243      P=0.085      P=0.022 *    P=0.278      |
|LOGISTIC REGRESSION|     P=0.144      P=0.050      P=0.017 *    P=0.437     |P=0.108      P=0.019 *    P=0.051      P=0.117      |
|COCH-ARM / FISHERS |     P=0.082N     P=0.025 *    P=0.008 **   P=0.242N    |P=0.417N     P=0.077      P=0.013 *    P=0.586N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Metaplasia Osseous                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/49 (4%)    1/50 (2%)    0/50 (0%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/49 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     4.4%         2.1%         0.0%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/35 (3%)    1/43 (2%)    0/43 (0%)    0/22 (0%)   |0/35 (0%)    0/35 (0%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     670          729 (T)      ---          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.131N     P=0.447N     P=0.210N     P=0.363N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.096N     P=0.482N     P=0.229N     P=0.329N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.100N     P=0.486N     P=0.232N     P=0.290N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.096N     P=0.475N     P=0.224N     P=0.366N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.118N     P=0.494N     P=0.234N     P=0.321N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.099N     P=0.492N     P=0.242N     P=0.242N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 12
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     43/49 (88%)  49/50 (98%)  47/50 (94%)  36/50 (72%) |5/50 (10%)   5/50 (10%)   5/49 (10%)   6/50 (12%)   |
|POLY-3 ADJUSTED (b)|     89.6%        98.7%        95.5%        87.5%       |11.0%        11.5%        10.6%        16.4%        |
|TERMINAL (d)       |     33/35 (94%)  43/43 (100%) 41/43 (95%)  20/22 (91%) |4/35 (11%)   3/35 (9%)    4/43 (9%)    3/25 (12%)   |
|FIRST INCIDENCE    |     501          563          439          481         |671          638          653          343          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.019 *    P=0.373N     P=0.242N     P=0.066     |P=0.246      P=0.623      P=0.511N     P=0.314      |
|POLY 3             |     P=0.279N     P=0.050      P=0.220      P=0.511N    |P=0.303      P=0.602      P=0.604N     P=0.351      |
|POLY 1.5           |     P=0.062N     P=0.051      P=0.211      P=0.244N    |P=0.340      P=0.608      P=0.619N     P=0.403      |
|POLY 6             |     P=0.562      P=0.052      P=0.268      P=0.546     |P=0.279      P=0.607      P=0.581N     P=0.312      |
|LOGISTIC REGRESSION|     P=0.557N     P=0.079      P=0.215      P=0.579     |P=0.376      P=0.603      P=0.615N     P=0.478      |
|COCH-ARM / FISHERS |     P=0.002N**   P=0.053      P=0.233      P=0.044N*   |P=0.421      P=0.630N     P=0.617      P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney                                                                                                                           |
|     Nephropathy                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     43/49 (88%)  48/50 (96%)  47/50 (94%)  39/50 (78%) |15/50 (30%)  19/50 (38%)  22/49 (45%)  9/50 (18%)   |
|POLY-3 ADJUSTED (b)|     90.9%        96.7%        94.3%        91.7%       |33.1%        43.8%        46.4%        25.1%        |
|TERMINAL (d)       |     34/35 (97%)  43/43 (100%) 41/43 (95%)  22/22 (100%)|14/35 (40%)  17/35 (49%)  21/43 (49%)  7/25 (28%)   |
|FIRST INCIDENCE    |     513          563          429          481         |662          638          589          480          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.002 **   P=0.269N     P=0.226N     P=0.015 *   |P=0.316N     P=0.252      P=0.304      P=0.391N     |
|POLY 3             |     P=0.532N     P=0.198      P=0.400      P=0.620     |P=0.304N     P=0.204      P=0.134      P=0.297N     |
|POLY 1.5           |     P=0.255N     P=0.162      P=0.318      P=0.466N    |P=0.207N     P=0.217      P=0.115      P=0.224N     |
|POLY 6             |     P=0.353      P=0.264      P=0.529      P=0.358     |P=0.382N     P=0.209      P=0.165      P=0.361N     |
|LOGISTIC REGRESSION|     P=0.313      P=0.216      P=0.217      P=0.195     |P=0.340N     P=0.220      P=0.174      P=0.381N     |
|COCH-ARM / FISHERS |     P=0.030N*    P=0.128      P=0.233      P=0.154N    |P=0.082N     P=0.263      P=0.093      P=0.121N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 13
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Cortex                                                                                                                   |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     11/49 (22%)  12/50 (24%)  8/50 (16%)   9/50 (18%)  |2/50 (4%)    3/50 (6%)    1/49 (2%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     24.5%        25.0%        17.0%        26.8%       |4.4%         7.0%         2.1%         2.9%         |
|TERMINAL (d)       |     11/35 (31%)  11/43 (26%)  7/43 (16%)   5/22 (23%)  |2/35 (6%)    3/35 (9%)    1/43 (2%)    1/25 (4%)    |
|FIRST INCIDENCE    |     729 (T)      605          694          481         |730 (T)      730 (T)      730 (T)      730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.406      P=0.471N     P=0.156N     P=0.405     |P=0.365N     P=0.500      P=0.428N     P=0.617N     |
|POLY 3             |     P=0.502N     P=0.573      P=0.266N     P=0.512     |P=0.334N     P=0.478      P=0.486N     P=0.589N     |
|POLY 1.5           |     P=0.424N     P=0.551      P=0.279N     P=0.579N    |P=0.319N     P=0.483      P=0.494N     P=0.558N     |
|POLY 6             |     P=0.522      P=0.586N     P=0.240N     P=0.419     |P=0.339N     P=0.480      P=0.474N     P=0.613N     |
|LOGISTIC REGRESSION|     P=0.548      P=0.586N     P=0.188N     P=0.513     |P=0.365N     P=0.500      P=0.428N     P=0.617N     |
|COCH-ARM / FISHERS |     P=0.261N     P=0.522      P=0.288N     P=0.382N    |P=0.280N     P=0.500      P=0.508N     P=0.500N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Kidney: Renal Tubule                                                                                                             |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     9/49 (18%)   8/50 (16%)   9/50 (18%)   2/50 (4%)   |0/50 (0%)    0/50 (0%)    0/49 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     20.0%        16.8%        19.2%        6.4%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     8/35 (23%)   8/43 (19%)   9/43 (21%)   2/22 (9%)   |0/35 (0%)    0/35 (0%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     694          729 (T)      729 (T)      729 (T)     |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.114N     P=0.324N     P=0.416N     P=0.124N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.131N     P=0.451N     P=0.567N     P=0.099N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.078N     P=0.464N     P=0.578N     P=0.059N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.190N     P=0.432N     P=0.544N     P=0.149N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.129N     P=0.375N     P=0.471N     P=0.139N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.025N*    P=0.482N     P=0.584N     P=0.023N*   |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 14
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Basophilic Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    4/50 (8%)    6/50 (12%)   2/50 (4%)   |1/50 (2%)    7/50 (14%)   2/49 (4%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         8.3%         12.8%        6.3%        |2.2%         16.3%        4.3%         5.7%         |
|TERMINAL (d)       |     0/35 (0%)    3/43 (7%)    6/43 (14%)   1/22 (5%)   |1/35 (3%)    7/35 (20%)   2/43 (5%)    2/25 (8%)    |
|FIRST INCIDENCE    |     ---          563          729 (T)      481         |730 (T)      730 (T)      730 (T)      730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.147      P=0.089      P=0.031 *    P=0.189     |P=0.569N     P=0.031 *    P=0.572      P=0.383      |
|POLY 3             |     P=0.114      P=0.070      P=0.018 *    P=0.171     |P=0.549N     P=0.025 *    P=0.514      P=0.411      |
|POLY 1.5           |     P=0.182      P=0.067      P=0.017 *    P=0.194     |P=0.510N     P=0.026 *    P=0.506      P=0.442      |
|POLY 6             |     P=0.074      P=0.074      P=0.019 *    P=0.152     |P=0.551      P=0.025 *    P=0.526      P=0.386      |
|LOGISTIC REGRESSION|     P=0.243      P=0.048 *    P=0.031 *    P=0.281     |P=0.569N     P=0.031 *    P=0.572      P=0.383      |
|COCH-ARM / FISHERS |     P=0.351      P=0.061      P=0.014 *    P=0.253     |P=0.422N     P=0.030 *    P=0.492      P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Clear Cell Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     7/49 (14%)   10/50 (20%)  10/50 (20%)  4/50 (8%)   |3/50 (6%)    6/50 (12%)   6/49 (12%)   1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     15.6%        21.0%        21.4%        12.6%       |6.6%         13.7%        12.8%        2.9%         |
|TERMINAL (d)       |     7/35 (20%)   10/43 (23%)  10/43 (23%)  3/22 (14%)  |3/35 (9%)    4/35 (11%)   6/43 (14%)   1/25 (4%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      481         |730 (T)      521          730 (T)      730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.483N     P=0.472      P=0.472      P=0.537N    |P=0.311N     P=0.244      P=0.352      P=0.431N     |
|POLY 3             |     P=0.458N     P=0.343      P=0.330      P=0.485N    |P=0.348N     P=0.226      P=0.263      P=0.403N     |
|POLY 1.5           |     P=0.341N     P=0.331      P=0.320      P=0.392N    |P=0.289N     P=0.228      P=0.250      P=0.368N     |
|POLY 6             |     P=0.522      P=0.362      P=0.353      P=0.569N    |P=0.394N     P=0.232      P=0.280      P=0.433N     |
|LOGISTIC REGRESSION|     P=0.534N     P=0.472      P=0.472      P=0.558N    |P=0.301N     P=0.226      P=0.352      P=0.431N     |
|COCH-ARM / FISHERS |     P=0.160N     P=0.314      P=0.314      P=0.251N    |P=0.191N     P=0.243      P=0.233      P=0.309N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 15
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Eosinophilic Focus                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     16/49 (33%)  10/50 (20%)  12/50 (24%)  3/50 (6%)   |9/50 (18%)   3/50 (6%)    11/49 (22%)  3/50 (6%)    |
|POLY-3 ADJUSTED (b)|     34.7%        21.0%        25.6%        9.6%        |19.9%        7.0%         23.2%        8.4%         |
|TERMINAL (d)       |     12/35 (34%)  10/43 (23%)  12/43 (28%)  2/22 (9%)   |8/35 (23%)   3/35 (9%)    10/43 (23%)  2/25 (8%)    |
|FIRST INCIDENCE    |     583          729 (T)      729 (T)      710         |687          730 (T)      589          480          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.020N*    P=0.048N*    P=0.110N     P=0.027N*   |P=0.281N     P=0.061N     P=0.592      P=0.162N     |
|POLY 3             |     P=0.021N*    P=0.105N     P=0.234N     P=0.013N*   |P=0.279N     P=0.071N     P=0.447      P=0.133N     |
|POLY 1.5           |     P=0.009N**   P=0.109N     P=0.237N     P=0.004N**  |P=0.226N     P=0.068N     P=0.420      P=0.102N     |
|POLY 6             |     P=0.042N*    P=0.101N     P=0.224N     P=0.033N*   |P=0.324N     P=0.069N     P=0.484      P=0.163N     |
|LOGISTIC REGRESSION|     P=0.023N*    P=0.098N     P=0.213N     P=0.017N*   |P=0.268N     P=0.061N     P=0.458      P=0.141N     |
|COCH-ARM / FISHERS |     P<0.001N**   P=0.115N     P=0.232N     P<0.001N**  |P=0.145N     P=0.061N     P=0.382      P=0.061N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Hematopoietic Cell Proliferation                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    0/50 (0%)    3/50 (6%)    1/50 (2%)   |2/50 (4%)    2/50 (4%)    6/49 (12%)   2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         6.3%         3.2%        |4.4%         4.7%         12.6%        5.7%         |
|TERMINAL (d)       |     0/35 (0%)    0/43 (0%)    2/43 (5%)    1/22 (5%)   |2/35 (6%)    2/35 (6%)    5/43 (12%)   0/25 (0%)    |
|FIRST INCIDENCE    |     ---          ---          439          729 (T)     |730 (T)      730 (T)      589          641          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.155      (e)          P=0.148      P=0.407     |P=0.345      P=0.695      P=0.202      P=0.569      |
|POLY 3             |     P=0.097      (e)          P=0.130      P=0.429     |P=0.319      P=0.677      P=0.150      P=0.602      |
|POLY 1.5           |     P=0.144      (e)          P=0.126      P=0.456     |P=0.379      P=0.680      P=0.140      P=0.634      |
|POLY 6             |     P=0.072      (e)          P=0.136      P=0.405     |P=0.279      P=0.679      P=0.164      P=0.577      |
|LOGISTIC REGRESSION|     P=0.297      (e)          P=0.138      P=0.407     |P=0.388      P=0.695      P=0.132      P=0.611      |
|COCH-ARM / FISHERS |     P=0.251      (e)          P=0.125      P=0.505     |P=0.499      P=0.691N     P=0.128      P=0.691N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 16
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Infiltration Cellular Mononuclear Cell                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     9/49 (18%)   11/50 (22%)  7/50 (14%)   6/50 (12%)  |30/50 (60%)  36/50 (72%)  40/49 (82%)  30/50 (60%)  |
|POLY-3 ADJUSTED (b)|     19.6%        23.1%        14.9%        18.9%       |65.2%        80.2%        84.1%        70.0%        |
|TERMINAL (d)       |     6/35 (17%)   11/43 (26%)  7/43 (16%)   5/22 (23%)  |26/35 (74%)  30/35 (86%)  38/43 (88%)  18/25 (72%)  |
|FIRST INCIDENCE    |     513          729 (T)      729 (T)      481         |607          422          589          480          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.492N     P=0.582      P=0.258N     P=0.569     |P=0.045 *    P=0.134      P=0.302      P=0.073      |
|POLY 3             |     P=0.384N     P=0.436      P=0.376N     P=0.582N    |P=0.405      P=0.073      P=0.024 *    P=0.397      |
|POLY 1.5           |     P=0.297N     P=0.430      P=0.379N     P=0.461N    |P=0.458      P=0.088      P=0.019 *    P=0.445      |
|POLY 6             |     P=0.451N     P=0.446      P=0.362N     P=0.531     |P=0.392      P=0.075      P=0.034 *    P=0.384      |
|LOGISTIC REGRESSION|     P=0.444N     P=0.439      P=0.372N     P=0.558N    |P=0.149      P=0.052      P=0.055      P=0.287      |
|COCH-ARM / FISHERS |     P=0.150N     P=0.421      P=0.376N     P=0.274N    |P=0.466N     P=0.146      P=0.016 *    P=0.581N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     22/49 (45%)  21/50 (42%)  19/50 (38%)  21/50 (42%) |32/50 (64%)  36/50 (72%)  41/49 (84%)  38/50 (76%)  |
|POLY-3 ADJUSTED (b)|     47.2%        43.8%        40.0%        53.5%       |70.3%        80.4%        86.2%        87.0%        |
|TERMINAL (d)       |     17/35 (49%)  20/43 (47%)  17/43 (40%)  9/22 (41%)  |31/35 (89%)  32/35 (91%)  39/43 (91%)  23/25 (92%)  |
|FIRST INCIDENCE    |     501          625          612          481         |607          521          589          480          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.076      P=0.217N     P=0.134N     P=0.145     |P<0.001 **   P=0.174      P=0.409      P<0.001 **   |
|POLY 3             |     P=0.341      P=0.451N     P=0.310N     P=0.357     |P=0.023 *    P=0.176      P=0.041 *    P=0.033 *    |
|POLY 1.5           |     P=0.435      P=0.457N     P=0.317N     P=0.470     |P=0.032 *    P=0.186      P=0.031 *    P=0.050      |
|POLY 6             |     P=0.282      P=0.441N     P=0.286N     P=0.274     |P=0.023 *    P=0.211      P=0.068      P=0.031 *    |
|LOGISTIC REGRESSION|     P=0.540      P=0.424N     P=0.301N     P=0.517N    |P<0.001 **   P=0.107      P=0.107      P=0.005 **   |
|COCH-ARM / FISHERS |     P=0.424N     P=0.465N     P=0.311N     P=0.465N    |P=0.097      P=0.260      P=0.022 *    P=0.138      |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 17
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Mixed Cell Focus                                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    11/50 (22%)  11/50 (22%)  2/50 (4%)   |3/50 (6%)    1/50 (2%)    3/49 (6%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         23.1%        23.2%        6.4%        |6.6%         2.3%         6.4%         0.0%         |
|TERMINAL (d)       |     0/35 (0%)    11/43 (26%)  10/43 (23%)  2/22 (9%)   |3/35 (9%)    1/35 (3%)    3/43 (7%)    0/25 (0%)    |
|FIRST INCIDENCE    |     ---          729 (T)      502          729 (T)     |730 (T)      730 (T)      730 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.265      P=0.002 **   P=0.002 **   P=0.143     |P=0.180N     P=0.305N     P=0.565N     P=0.186N     |
|POLY 3             |     P=0.168      P<0.001 **   P<0.001 **   P=0.167     |P=0.194N     P=0.323N     P=0.643N     P=0.172N     |
|POLY 1.5           |     P=0.315      P<0.001 **   P<0.001 **   P=0.192     |P=0.173N     P=0.319N     P=0.655N     P=0.152N     |
|POLY 6             |     P=0.089      P<0.001 **   P<0.001 **   P=0.147     |P=0.212N     P=0.320N     P=0.627N     P=0.191N     |
|LOGISTIC REGRESSION|     P=0.258      P=0.002 **   P<0.001 **   P=0.143     |P=0.180N     P=0.305N     P=0.565N     (e)          |
|COCH-ARM / FISHERS |     P=0.488N     P<0.001 **   P<0.001 **   P=0.253     |P=0.136N     P=0.309N     P=0.651      P=0.121N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     6/49 (12%)   5/50 (10%)   1/50 (2%)    0/50 (0%)   |3/50 (6%)    2/50 (4%)    2/49 (4%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     12.8%        10.3%        2.1%         0.0%        |6.6%         4.7%         4.2%         2.8%         |
|TERMINAL (d)       |     1/35 (3%)    2/43 (5%)    0/43 (0%)    0/22 (0%)   |2/35 (6%)    2/35 (6%)    1/43 (2%)    0/25 (0%)    |
|FIRST INCIDENCE    |     501          625          655          ---         |623          730 (T)      701          343          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.015N*    P=0.432N     P=0.054N     P=0.082N    |P=0.312N     P=0.508N     P=0.430N     P=0.409N     |
|POLY 3             |     P=0.009N**   P=0.476N     P=0.055N     P=0.055N    |P=0.288N     P=0.526N     P=0.484N     P=0.397N     |
|POLY 1.5           |     P=0.007N**   P=0.480N     P=0.055N     P=0.034N*   |P=0.270N     P=0.519N     P=0.494N     P=0.363N     |
|POLY 6             |     P=0.012N*    P=0.468N     P=0.053N     P=0.084N    |P=0.299N     P=0.526N     P=0.470N     P=0.426N     |
|LOGISTIC REGRESSION|     P<0.001N**   P=0.613      P=0.037N*    P=0.006N**  |P=0.196N     P=0.518N     P=0.524N     P=0.179N     |
|COCH-ARM / FISHERS |     P=0.004N**   P=0.486N     P=0.053N     P=0.012N*   |P=0.233N     P=0.500N     P=0.510N     P=0.309N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 18
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Pigmentation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/49 (6%)    0/50 (0%)    2/50 (4%)    3/50 (6%)   |18/50 (36%)  12/50 (24%)  17/49 (35%)  7/50 (14%)   |
|POLY-3 ADJUSTED (b)|     6.7%         0.0%         4.2%         9.4%        |39.8%        27.9%        36.2%        20.1%        |
|TERMINAL (d)       |     3/35 (9%)    0/43 (0%)    1/43 (2%)    2/22 (9%)   |17/35 (49%)  12/35 (34%)  17/43 (40%)  7/25 (28%)   |
|FIRST INCIDENCE    |     729 (T)      ---          612          481         |704          730 (T)      730 (T)      730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.233      P=0.087N     P=0.422N     P=0.476     |P=0.073N     P=0.120N     P=0.214N     P=0.068N     |
|POLY 3             |     P=0.305      P=0.109N     P=0.477N     P=0.496     |P=0.080N     P=0.167N     P=0.443N     P=0.049N*    |
|POLY 1.5           |     P=0.335      P=0.112N     P=0.485N     P=0.563     |P=0.050N     P=0.161N     P=0.478N     P=0.027N*    |
|POLY 6             |     P=0.298      P=0.105N     P=0.461N     P=0.436     |P=0.110N     P=0.161N     P=0.393N     P=0.075N     |
|LOGISTIC REGRESSION|     P=0.378      (e)          P=0.491N     P=0.520     |P=0.083N     P=0.112N     P=0.252N     P=0.070N     |
|COCH-ARM / FISHERS |     P=0.410      P=0.117N     P=0.490N     P=0.651N    |P=0.018N*    P=0.138N     P=0.530N     P=0.010N*    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver                                                                                                                            |
|     Tension Lipidosis                                                                                                           |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/49 (2%)    0/50 (0%)    1/50 (2%)    0/50 (0%)   |2/50 (4%)    3/50 (6%)    0/49 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     2.2%         0.0%         2.1%         0.0%        |4.4%         6.9%         0.0%         0.0%         |
|TERMINAL (d)       |     1/35 (3%)    0/43 (0%)    1/43 (2%)    0/22 (0%)   |1/35 (3%)    2/35 (6%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     729 (T)      ---          729 (T)      ---         |727          556          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.492N     P=0.459N     P=0.715N     P=0.593N    |P=0.096N     P=0.490      P=0.199N     P=0.320N     |
|POLY 3             |     P=0.447N     P=0.488N     P=0.751N     P=0.571N    |P=0.085N     P=0.484      P=0.228N     P=0.299N     |
|POLY 1.5           |     P=0.435N     P=0.492N     P=0.754N     P=0.543N    |P=0.082N     P=0.486      P=0.234N     P=0.276N     |
|POLY 6             |     P=0.476N     P=0.484N     P=0.745N     P=0.595N    |P=0.084N     P=0.489      P=0.221N     P=0.319N     |
|LOGISTIC REGRESSION|     P=0.492N     (e)          P=0.715N     (e)         |P=0.077N     P=0.494      P=0.203N     P=0.316N     |
|COCH-ARM / FISHERS |     P=0.402N     P=0.495N     P=0.747N     P=0.495N    |P=0.074N     P=0.500      P=0.253N     P=0.247N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 19
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Liver: Hepatocyte                                                                                                                |
|     Vacuolization Cytoplasmic                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     6/49 (12%)   10/50 (20%)  9/50 (18%)   16/50 (32%) |7/50 (14%)   9/50 (18%)   3/49 (6%)    18/50 (36%)  |
|POLY-3 ADJUSTED (b)|     13.2%        21.0%        19.2%        40.4%       |14.9%        20.1%        6.4%         42.4%        |
|TERMINAL (d)       |     5/35 (14%)   10/43 (23%)  9/43 (21%)   4/22 (18%)  |2/35 (6%)    5/35 (14%)   3/43 (7%)    8/25 (32%)   |
|FIRST INCIDENCE    |     501          729 (T)      729 (T)      481         |492          374          730 (T)      212          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.344      P=0.436      P=0.004 **  |P<0.001 **   P=0.372      P=0.123N     P=0.003 **   |
|POLY 3             |     P=0.003 **   P=0.233      P=0.307      P=0.003 **  |P=0.002 **   P=0.350      P=0.158N     P=0.003 **   |
|POLY 1.5           |     P=0.005 **   P=0.227      P=0.302      P=0.005 **  |P=0.002 **   P=0.362      P=0.161N     P=0.004 **   |
|POLY 6             |     P=0.002 **   P=0.244      P=0.323      P=0.002 **  |P=0.002 **   P=0.348      P=0.152N     P=0.002 **   |
|LOGISTIC REGRESSION|     P=0.064      P=0.234      P=0.311      P=0.142     |P=0.047 *    P=0.466      P=0.245N     P=0.100      |
|COCH-ARM / FISHERS |     P=0.013 *    P=0.220      P=0.303      P=0.016 *   |P=0.004 **   P=0.393      P=0.167N     P=0.010 *    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/49 (4%)    3/50 (6%)    0/50 (0%)    4/50 (8%)   |2/50 (4%)    1/50 (2%)    3/50 (6%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     4.4%         6.2%         0.0%         12.7%       |4.4%         2.3%         6.3%         2.9%         |
|TERMINAL (d)       |     0/35 (0%)    2/43 (5%)    0/43 (0%)    3/22 (14%)  |1/35 (3%)    0/35 (0%)    2/43 (5%)    0/25 (0%)    |
|FIRST INCIDENCE    |     501          563          ---          623         |645          422          701          703          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.115      P=0.546      P=0.237N     P=0.131     |P=0.579N     P=0.516N     P=0.574      P=0.625N     |
|POLY 3             |     P=0.239      P=0.522      P=0.232N     P=0.188     |P=0.572N     P=0.513N     P=0.522      P=0.590N     |
|POLY 1.5           |     P=0.253      P=0.516      P=0.234N     P=0.240     |P=0.539N     P=0.510N     P=0.513      P=0.559N     |
|POLY 6             |     P=0.248      P=0.531      P=0.228N     P=0.149     |P=0.558      P=0.511N     P=0.534      P=0.615N     |
|LOGISTIC REGRESSION|     P=0.358      P=0.320      P=0.146N     P=0.274     |P=0.438N     P=0.398N     P=0.499      P=0.572N     |
|COCH-ARM / FISHERS |     P=0.308      P=0.510      P=0.242N     P=0.349     |P=0.474N     P=0.500N     P=0.500      P=0.500N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 20
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/49 (6%)    1/50 (2%)    0/50 (0%)    2/50 (4%)   |5/50 (10%)   1/50 (2%)    2/50 (4%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     6.6%         2.1%         0.0%         6.4%        |11.0%        2.3%         4.2%         5.6%         |
|TERMINAL (d)       |     2/35 (6%)    1/43 (2%)    0/43 (0%)    2/22 (9%)   |3/35 (9%)    1/35 (3%)    2/43 (5%)    1/25 (4%)    |
|FIRST INCIDENCE    |     650          729 (T)      ---          729 (T)     |662          730 (T)      730 (T)      480          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.621N     P=0.254N     P=0.097N     P=0.643     |P=0.309N     P=0.110N     P=0.157N     P=0.353N     |
|POLY 3             |     P=0.424N     P=0.287N     P=0.112N     P=0.662N    |P=0.251N     P=0.115N     P=0.200N     P=0.329N     |
|POLY 1.5           |     P=0.443N     P=0.292N     P=0.114N     P=0.600N    |P=0.243N     P=0.112N     P=0.206N     P=0.287N     |
|POLY 6             |     P=0.402N     P=0.281N     P=0.108N     P=0.628     |P=0.255N     P=0.116N     P=0.191N     P=0.367N     |
|LOGISTIC REGRESSION|     P=0.606N     P=0.297N     P=0.117N     P=0.649     |P=0.248N     P=0.112N     P=0.206N     P=0.248N     |
|COCH-ARM / FISHERS |     P=0.438N     P=0.301N     P=0.117N     P=0.490N    |P=0.221N     P=0.102N     P=0.218N     P=0.218N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung                                                                                                                             |
|     Thrombosis                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/49 (6%)    2/50 (4%)    1/50 (2%)    1/50 (2%)   |0/50 (0%)    1/50 (2%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     6.5%         4.2%         2.1%         3.2%        |0.0%         2.3%         2.1%         0.0%         |
|TERMINAL (d)       |     0/35 (0%)    1/43 (2%)    1/43 (2%)    0/22 (0%)   |0/35 (0%)    0/35 (0%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     583          605          729 (T)      623         |---          374          533          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.352N     P=0.465N     P=0.285N     P=0.546N    |P=0.638N     P=0.500      P=0.508      (e)          |
|POLY 3             |     P=0.251N     P=0.482N     P=0.300N     P=0.452N    |P=0.651      P=0.494      P=0.513      (e)          |
|POLY 1.5           |     P=0.236N     P=0.486N     P=0.301N     P=0.392N    |P=0.634N     P=0.495      P=0.508      (e)          |
|POLY 6             |     P=0.264N     P=0.477N     P=0.296N     P=0.506N    |P=0.613      P=0.496      P=0.520      (e)          |
|LOGISTIC REGRESSION|     P=0.085N     P=0.690N     P=0.258N     P=0.190N    |P=0.310N     P=0.769      P=0.280      (e)          |
|COCH-ARM / FISHERS |     P=0.194N     P=0.490N     P=0.301N     P=0.301N    |P=0.595N     P=0.500      P=0.500      (e)          |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 21
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung: Alveolar Epithelium                                                                                                        |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/49 (6%)    6/50 (12%)   5/50 (10%)   4/50 (8%)   |1/50 (2%)    1/50 (2%)    1/50 (2%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     6.6%         12.6%        10.7%        12.6%       |2.2%         2.3%         2.1%         0.0%         |
|TERMINAL (d)       |     2/35 (6%)    6/43 (14%)   5/43 (12%)   2/22 (9%)   |1/35 (3%)    0/35 (0%)    1/43 (2%)    0/25 (0%)    |
|FIRST INCIDENCE    |     663          729 (T)      729 (T)      481         |730 (T)      644          730 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.253      P=0.342      P=0.462      P=0.286     |P=0.373N     P=0.752      P=0.715N     P=0.567N     |
|POLY 3             |     P=0.291      P=0.269      P=0.377      P=0.319     |P=0.355N     P=0.752      P=0.749N     P=0.551N     |
|POLY 1.5           |     P=0.372      P=0.262      P=0.371      P=0.387     |P=0.342N     P=0.753      P=0.753N     P=0.533N     |
|POLY 6             |     P=0.240      P=0.278      P=0.390      P=0.263     |P=0.363N     P=0.754      P=0.742N     P=0.565N     |
|LOGISTIC REGRESSION|     P=0.286      P=0.284      P=0.391      P=0.356     |P=0.341N     P=0.763N     P=0.715N     (e)          |
|COCH-ARM / FISHERS |     P=0.544      P=0.254      P=0.369      P=0.511     |P=0.311N     P=0.753N     P=0.753N     P=0.500N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Lung: Alveolus                                                                                                                   |
|     Infiltration Cellular Histiocyte                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/49 (8%)    8/50 (16%)   3/50 (6%)    3/50 (6%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    2/50 (4%)    |
|POLY-3 ADJUSTED (b)|     8.9%         16.6%        6.3%         9.4%        |2.2%         0.0%         0.0%         5.7%         |
|TERMINAL (d)       |     3/35 (9%)    6/43 (14%)   1/43 (2%)    2/22 (9%)   |1/35 (3%)    0/35 (0%)    0/43 (0%)    1/25 (4%)    |
|FIRST INCIDENCE    |     663          563          612          481         |730 (T)      ---          ---          694          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.478N     P=0.281      P=0.426N     P=0.588     |P=0.175      P=0.500N     P=0.459N     P=0.388      |
|POLY 3             |     P=0.382N     P=0.210      P=0.472N     P=0.619     |P=0.233      P=0.510N     P=0.490N     P=0.412      |
|POLY 1.5           |     P=0.327N     P=0.201      P=0.482N     P=0.613N    |P=0.235      P=0.507N     P=0.494N     P=0.443      |
|POLY 6             |     P=0.420N     P=0.223      P=0.454N     P=0.553     |P=0.234      P=0.509N     P=0.484N     P=0.389      |
|LOGISTIC REGRESSION|     P=0.269N     P=0.183      P=0.489N     P=0.656N    |P=0.179      (e)          (e)          P=0.383      |
|COCH-ARM / FISHERS |     P=0.218N     P=0.188      P=0.489N     P=0.489N    |P=0.246      P=0.500N     P=0.500N     P=0.500      |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 22
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mandibular                                                                                                           |
|     Hyperplasia Lymphoid                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/46 (2%)    1/48 (2%)    0/50 (0%)    0/47 (0%)   |5/48 (10%)   4/49 (8%)    3/46 (7%)    1/47 (2%)    |
|POLY-3 ADJUSTED (b)|     2.4%         2.2%         0.0%         0.0%        |11.4%        9.3%         6.9%         3.1%         |
|TERMINAL (d)       |     1/33 (3%)    1/42 (2%)    0/43 (0%)    0/22 (0%)   |5/35 (14%)   4/35 (11%)   3/39 (8%)    1/24 (4%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      ---          ---         |730 (T)      730 (T)      730 (T)      730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.275N     P=0.707N     P=0.447N     P=0.581N    |P=0.123N     P=0.500N     P=0.297N     P=0.207N     |
|POLY 3             |     P=0.223N     P=0.740N     P=0.479N     P=0.568N    |P=0.120N     P=0.515N     P=0.360N     P=0.185N     |
|POLY 1.5           |     P=0.231N     P=0.745N     P=0.482N     P=0.542N    |P=0.103N     P=0.508N     P=0.368N     P=0.153N     |
|POLY 6             |     P=0.223N     P=0.734N     P=0.473N     P=0.591N    |P=0.133N     P=0.515N     P=0.350N     P=0.215N     |
|LOGISTIC REGRESSION|     P=0.275N     P=0.707N     (e)          (e)         |P=0.123N     P=0.500N     P=0.297N     P=0.207N     |
|COCH-ARM / FISHERS |     P=0.230N     P=0.742N     P=0.479N     P=0.495N    |P=0.072N     P=0.487N     P=0.381N     P=0.107N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mandibular                                                                                                           |
|     Pigmentation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/46 (0%)    0/48 (0%)    0/50 (0%)    0/47 (0%)   |3/48 (6%)    16/49 (33%)  9/46 (20%)   4/47 (9%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |6.8%         36.7%        20.6%        12.2%        |
|TERMINAL (d)       |     0/33 (0%)    0/42 (0%)    0/43 (0%)    0/22 (0%)   |2/35 (6%)    13/35 (37%)  8/39 (21%)   4/24 (17%)   |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |671          476          716          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.527N     P<0.001 **   P=0.095      P=0.305      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.509      P<0.001 **   P=0.056      P=0.342      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.471N     P<0.001 **   P=0.054      P=0.393      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.415      P<0.001 **   P=0.058      P=0.300      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.543N     P<0.001 **   P=0.063      P=0.291      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.282N     P<0.001 **   P=0.051      P=0.488      |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 23
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mediastinal                                                                                                          |
|     Hyperplasia Lymphoid                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)   |1/50 (2%)    0/50 (0%)    2/50 (4%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |2.2%         0.0%         4.2%         0.0%         |
|TERMINAL (d)       |     0/35 (0%)    0/43 (0%)    0/43 (0%)    0/22 (0%)   |1/35 (3%)    0/35 (0%)    2/43 (5%)    0/25 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |730 (T)      ---          730 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.533N     P=0.500N     P=0.572      P=0.567N     |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.533N     P=0.510N     P=0.518      P=0.551N     |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.508N     P=0.507N     P=0.511      P=0.533N     |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.554N     P=0.509N     P=0.529      P=0.565N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.533N     (e)          P=0.572      (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.461N     P=0.500N     P=0.500      P=0.500N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mesenteric                                                                                                           |
|     Ectasia                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/46 (0%)    0/43 (0%)    0/49 (0%)    0/47 (0%)   |2/47 (4%)    0/48 (0%)    0/47 (0%)    0/46 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |4.6%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/35 (0%)    0/38 (0%)    0/42 (0%)    0/22 (0%)   |2/34 (6%)    0/35 (0%)    0/40 (0%)    0/24 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |730 (T)      ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.128N     P=0.232N     P=0.203N     P=0.318N     |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.095N     P=0.246N     P=0.229N     P=0.305N     |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.103N     P=0.243N     P=0.233N     P=0.281N     |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.088N     P=0.245N     P=0.225N     P=0.324N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.128N     (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.116N     P=0.242N     P=0.247N     P=0.253N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 24
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mesenteric                                                                                                           |
|     Hemorrhage                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/46 (2%)    0/43 (0%)    0/49 (0%)    0/47 (0%)   |2/47 (4%)    1/48 (2%)    0/47 (0%)    0/46 (0%)    |
|POLY-3 ADJUSTED (b)|     2.4%         0.0%         0.0%         0.0%        |4.6%         2.4%         0.0%         0.0%         |
|TERMINAL (d)       |     1/35 (3%)    0/38 (0%)    0/42 (0%)    0/22 (0%)   |2/34 (6%)    1/35 (3%)    0/40 (0%)    0/24 (0%)    |
|FIRST INCIDENCE    |     729 (T)      ---          ---          ---         |730 (T)      730 (T)      ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.342N     P=0.484N     P=0.464N     P=0.593N    |P=0.118N     P=0.490N     P=0.203N     P=0.318N     |
|POLY 3             |     P=0.243N     P=0.505N     P=0.485N     P=0.568N    |P=0.099N     P=0.513N     P=0.229N     P=0.305N     |
|POLY 1.5           |     P=0.269N     P=0.509N     P=0.486N     P=0.542N    |P=0.101N     P=0.508N     P=0.233N     P=0.281N     |
|POLY 6             |     P=0.230N     P=0.500N     P=0.480N     P=0.590N    |P=0.095N     P=0.512N     P=0.225N     P=0.324N     |
|LOGISTIC REGRESSION|     P=0.342N     (e)          (e)          (e)         |P=0.118N     P=0.490N     (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.299N     P=0.517N     P=0.484N     P=0.495N    |P=0.103N     P=0.492N     P=0.247N     P=0.253N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Lymph Node, Mesenteric                                                                                                           |
|     Hyperplasia Lymphoid                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/46 (2%)    1/43 (2%)    1/49 (2%)    0/47 (0%)   |2/47 (4%)    0/48 (0%)    1/47 (2%)    1/46 (2%)    |
|POLY-3 ADJUSTED (b)|     2.4%         2.4%         2.2%         0.0%        |4.6%         0.0%         2.2%         3.1%         |
|TERMINAL (d)       |     1/35 (3%)    1/38 (3%)    1/42 (2%)    0/22 (0%)   |2/34 (6%)    0/35 (0%)    1/40 (3%)    1/24 (4%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      ---         |730 (T)      ---          730 (T)      730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.395N     P=0.743N     P=0.721N     P=0.593N    |P=0.596N     P=0.232N     P=0.443N     P=0.621N     |
|POLY 3             |     P=0.367N     P=0.755      P=0.743N     P=0.568N    |P=0.518N     P=0.246N     P=0.488N     P=0.596N     |
|POLY 1.5           |     P=0.346N     P=0.751      P=0.745N     P=0.542N    |P=0.517N     P=0.243N     P=0.493N     P=0.565N     |
|POLY 6             |     P=0.391N     P=0.760      P=0.739N     P=0.590N    |P=0.516N     P=0.245N     P=0.481N     P=0.621N     |
|LOGISTIC REGRESSION|     P=0.395N     P=0.743N     P=0.721N     (e)         |P=0.596N     (e)          P=0.443N     P=0.621N     |
|COCH-ARM / FISHERS |     P=0.300N     P=0.736      P=0.737N     P=0.495N    |P=0.509N     P=0.242N     P=0.500N     P=0.508N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 25
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Mammary Gland                                                                                                                    |
|     Hyperplasia Cystic                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/2 (0%)    |3/49 (6%)    1/50 (2%)    0/49 (0%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |6.8%         2.3%         0.0%         0.0%         |
|TERMINAL (d)       |     0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)    |3/35 (9%)    0/35 (0%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |730 (T)      711          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.051N     P=0.302N     P=0.087N     P=0.186N     |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.040N*    P=0.316N     P=0.109N     P=0.170N     |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.042N*    P=0.312N     P=0.113N     P=0.150N     |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.038N*    P=0.314N     P=0.103N     P=0.188N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.054N     P=0.309N     (e)          (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.044N*    P=0.301N     P=0.121N     P=0.121N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery                                                                                                                        |
|     Fibrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/3 (33%)    1/6 (17%)    0/6 (0%)     0/1 (0%)    |8/16 (50%)   7/11 (64%)   10/15 (67%)  2/4 (50%)    |
|POLY-3 ADJUSTED (b)|     36.0%        20.4%        0.0%         0.0%        |54.5%        69.6%        71.1%        52.9%        |
|TERMINAL (d)       |     1/2 (50%)    0/2 (0%)     0/5 (0%)     0/0 (0%)    |6/10 (60%)   6/9 (67%)    10/11 (91%)  2/3 (67%)    |
|FIRST INCIDENCE    |     729 (T)      563          ---          ---         |709          638          730 (T)      730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.302N     P=0.749N     P=0.318N     P=1.000     |P=0.500N     P=0.596N     P=0.490      P=0.439N     |
|POLY 3             |     P=0.183N     P=0.639N     P=0.348N     P=0.786N    |P=0.485      P=0.369      P=0.292      P=0.697N     |
|POLY 1.5           |     P=0.187N     P=0.621N     P=0.350N     P=0.753N    |P=0.471      P=0.349      P=0.288      P=0.699N     |
|POLY 6             |     P=0.174N     P=0.667N     P=0.343N     P=0.815N    |P=0.500      P=0.431      P=0.301      P=0.696N     |
|LOGISTIC REGRESSION|     P=0.191N     P=0.492N     (e)          (e)         |P=0.555      P=0.395      P=0.388      P=0.694N     |
|COCH-ARM / FISHERS |     P=0.284N     P=0.583N     P=0.333N     P=0.750N    |P=0.445      P=0.381      P=0.283      P=0.709N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 26
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery                                                                                                                        |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/3 (33%)    1/6 (17%)    1/6 (17%)    1/1 (100%)  |5/16 (31%)   6/11 (55%)   8/15 (53%)   0/4 (0%)     |
|POLY-3 ADJUSTED (b)|     36.0%        23.0%        17.9%        100.0%      |34.1%        59.6%        55.3%        0.0%         |
|TERMINAL (d)       |     1/2 (50%)    1/2 (50%)    1/5 (20%)    0/0 (0%)    |4/10 (40%)   5/9 (56%)    6/11 (55%)   0/3 (0%)     |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      481         |709          638          653          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.381      P=0.807      P=0.549N     P=0.382     |P=0.256N     P=0.425      P=0.328      P=0.174N     |
|POLY 3             |     P=0.426      P=0.674N     P=0.601N     P=0.525     |P=0.398N     P=0.198      P=0.217      P=0.244N     |
|POLY 1.5           |     P=0.408      P=0.639N     P=0.601N     P=0.513     |P=0.417N     P=0.188      P=0.203      P=0.252N     |
|POLY 6             |     P=0.457      P=0.729N     P=0.596N     P=0.548     |P=0.374N     P=0.231      P=0.243      P=0.235N     |
|LOGISTIC REGRESSION|     P=0.406      P=0.807      P=0.549N     (e)         |P=0.403N     P=0.197      P=0.221      P=0.229N     |
|COCH-ARM / FISHERS |     P=0.386      P=0.583N     P=0.583N     P=0.500     |P=0.445N     P=0.208      P=0.189      P=0.282N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery                                                                                                                        |
|     Inflammation Granulomatous                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/3 (0%)     0/6 (0%)     2/6 (33%)    0/1 (0%)    |0/16 (0%)    0/11 (0%)    0/15 (0%)    0/4 (0%)     |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         35.8%        0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/2 (0%)     0/2 (0%)     2/5 (40%)    0/0 (0%)    |0/10 (0%)    0/9 (0%)     0/11 (0%)    0/3 (0%)     |
|FIRST INCIDENCE    |     ---          ---          729 (T)      ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.379      (e)          P=0.451      (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.167      (e)          P=0.393      (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.198      (e)          P=0.393      (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.166      (e)          P=0.398      (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          P=0.451      (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.424      (e)          P=0.417      (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 27
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery                                                                                                                        |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/3 (0%)     1/6 (17%)    1/6 (17%)    0/1 (0%)    |5/16 (31%)   7/11 (64%)   12/15 (80%)  1/4 (25%)    |
|POLY-3 ADJUSTED (b)|     0.0%         23.0%        17.9%        0.0%        |34.3%        69.6%        80.9%        26.4%        |
|TERMINAL (d)       |     0/2 (0%)     1/2 (50%)    1/5 (20%)    0/0 (0%)    |4/10 (40%)   6/9 (67%)    10/11 (91%)  1/3 (33%)    |
|FIRST INCIDENCE    |     ---          729 (T)      729 (T)      ---         |727          638          589          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.731      P=0.500      P=0.682      (e)         |P=0.468      P=0.277      P=0.032 *    P=0.472N     |
|POLY 3             |     P=0.497      P=0.593      P=0.636      (e)         |P=0.257      P=0.085      P=0.007 **   P=0.625N     |
|POLY 1.5           |     P=0.516      P=0.613      P=0.635      (e)         |P=0.235      P=0.080      P=0.005 **   P=0.630N     |
|POLY 6             |     P=0.498      P=0.558      P=0.640      (e)         |P=0.288      P=0.107      P=0.010 *    P=0.618N     |
|LOGISTIC REGRESSION|     (e)          P=0.500      P=0.682      (e)         |P=0.260      P=0.096      P=0.010 *    P=0.611N     |
|COCH-ARM / FISHERS |     P=0.716      P=0.667      P=0.667      (e)         |P=0.225      P=0.102      P=0.008 **   P=0.657N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Mesentery: Fat                                                                                                                   |
|     Necrosis                                                                                                                    |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/3 (33%)    2/6 (33%)    1/6 (17%)    0/1 (0%)    |8/16 (50%)   7/11 (64%)   11/15 (73%)  3/4 (75%)    |
|POLY-3 ADJUSTED (b)|     36.0%        37.6%        17.9%        0.0%        |54.5%        69.6%        75.6%        79.3%        |
|TERMINAL (d)       |     1/2 (50%)    0/2 (0%)     1/5 (20%)    0/0 (0%)    |6/10 (60%)   6/9 (67%)    10/11 (91%)  3/3 (100%)   |
|FIRST INCIDENCE    |     729 (T)      563          729 (T)      ---         |709          638          589          730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.391N     P=0.522      P=0.549N     P=1.000N    |P=0.388      P=0.596N     P=0.344      P=0.651      |
|POLY 3             |     P=0.392N     P=0.744      P=0.601N     P=0.786N    |P=0.170      P=0.369      P=0.201      P=0.384      |
|POLY 1.5           |     P=0.367N     P=0.745      P=0.601N     P=0.753N    |P=0.162      P=0.349      P=0.185      P=0.379      |
|POLY 6             |     P=0.394N     P=0.745      P=0.596N     P=0.815N    |P=0.176      P=0.431      P=0.229      P=0.389      |
|LOGISTIC REGRESSION|     P=0.294N     P=0.559N     P=0.549N     (e)         |P=0.189      P=0.395      P=0.209      P=0.399      |
|COCH-ARM / FISHERS |     P=0.386N     P=0.762N     P=0.583N     P=0.750N    |P=0.147      P=0.381      P=0.168      P=0.375      |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 28
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose                                                                                                                             |
|     Foreign Body                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/49 (6%)    3/50 (6%)    4/50 (8%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     6.6%         6.3%         8.5%         3.2%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/35 (3%)    2/43 (5%)    3/43 (7%)    1/22 (5%)   |0/35 (0%)    0/35 (0%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     638          714          694          729 (T)     |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.448N     P=0.587N     P=0.582      P=0.510N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.430N     P=0.640N     P=0.519      P=0.450N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.361N     P=0.645N     P=0.513      P=0.390N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.496N     P=0.632N     P=0.531      P=0.505N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.412N     P=0.664      P=0.511      P=0.445N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.241N     P=0.651N     P=0.511      P=0.301N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose                                                                                                                             |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/49 (4%)    0/50 (0%)    3/50 (6%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     4.4%         0.0%         6.4%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/35 (3%)    0/43 (0%)    2/43 (5%)    0/22 (0%)   |0/35 (0%)    0/35 (0%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     638          ---          694          ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.434N     P=0.217N     P=0.568      P=0.371N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.438N     P=0.226N     P=0.517      P=0.329N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.384N     P=0.229N     P=0.512      P=0.291N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.501N     P=0.222N     P=0.529      P=0.367N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.367N     P=0.259N     P=0.509      P=0.285N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.291N     P=0.242N     P=0.510      P=0.242N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 29
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Nose: Nasolacrimal Duct                                                                                                          |
|     Inflammation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     4/49 (8%)    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)|     8.8%         0.0%         2.1%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     2/35 (6%)    0/43 (0%)    1/43 (2%)    0/22 (0%)   |0/35 (0%)    0/35 (0%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     501          ---          729 (T)      ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.060N     P=0.050N     P=0.143N     P=0.155N    |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.042N*    P=0.055N     P=0.171N     P=0.128N    |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.042N*    P=0.057N     P=0.174N     P=0.096N    |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.044N*    P=0.053N     P=0.165N     P=0.164N    |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.022N*    P=0.086N     P=0.166N     P=0.057N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.038N*    P=0.056N     P=0.175N     P=0.056N    |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Mucosa: Gingival                                                                                                            |
|     Foreign Body                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     27/31 (87%)  29/30 (97%)  26/27 (96%)  10/10 (100%)|2/3 (67%)    5/5 (100%)   1/2 (50%)    0/1 (0%)     |
|POLY-3 ADJUSTED (b)|     87.1%        96.7%        96.3%        100.0%      |72.3%        100.0%       50.0%        0.0%         |
|TERMINAL (d)       |     19/23 (83%)  24/25 (96%)  20/21 (95%)  6/6 (100%)  |2/2 (100%)   5/5 (100%)   1/2 (50%)    0/0 (0%)     |
|FIRST INCIDENCE    |     513          605          429          481         |730 (T)      730 (T)      730 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.375      P=0.574N     P=0.568      P=0.503     |P=0.500N     P=1.000      P=0.500N     P=1.000      |
|POLY 3             |     P=0.104      P=0.186      P=0.220      P=0.281     |P=0.132N     P=0.507      P=0.649N     P=0.511N     |
|POLY 1.5           |     P=0.104      P=0.186      P=0.220      P=0.281     |P=0.149N     P=0.445      P=0.660N     P=0.504N     |
|POLY 6             |     P=0.104      P=0.186      P=0.220      P=0.281     |P=0.105N     P=0.655      P=0.628N     P=0.530N     |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.500N     P=1.000      P=0.500N     (e)          |
|COCH-ARM / FISHERS |     P=0.104      P=0.187      P=0.222      P=0.311     |P=0.188N     P=0.375      P=0.700N     P=0.500N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 30
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Mucosa: Gingival                                                                                                            |
|     Inflammation Acute                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     9/31 (29%)   3/30 (10%)   10/27 (37%)  6/10 (60%)  |0/3 (0%)     0/5 (0%)     0/2 (0%)     0/1 (0%)     |
|POLY-3 ADJUSTED (b)|     29.9%        10.4%        38.7%        64.6%       |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     5/23 (22%)   2/25 (8%)    8/21 (38%)   3/6 (50%)   |0/2 (0%)     0/5 (0%)     0/2 (0%)     0/0 (0%)     |
|FIRST INCIDENCE    |     513          625          429          481         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.060      P=0.052N     P=0.452      P=0.209     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.016 *    P=0.060N     P=0.341      P=0.062     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.017 *    P=0.059N     P=0.347      P=0.067     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.016 *    P=0.060N     P=0.337      P=0.060     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.114      P=0.081N     P=0.387      P=0.302     |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.024 *    P=0.060N     P=0.356      P=0.084     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Oral Mucosa: Gingival                                                                                                            |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     19/31 (61%)  27/30 (90%)  16/27 (59%)  2/10 (20%)  |2/3 (67%)    5/5 (100%)   2/2 (100%)   0/1 (0%)     |
|POLY-3 ADJUSTED (b)|     64.5%        91.1%        62.0%        28.0%       |72.3%        100.0%       100.0%       0.0%         |
|TERMINAL (d)       |     15/23 (65%)  23/25 (92%)  12/21 (57%)  2/6 (33%)   |2/2 (100%)   5/5 (100%)   2/2 (100%)   0/0 (0%)     |
|FIRST INCIDENCE    |     638          605          502          729 (T)     |730 (T)      730 (T)      730 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.022N*    P=0.101      P=0.393N     P=0.046N*   |P=1.000N     P=1.000N     P=1.000N     P=1.000      |
|POLY 3             |     P=0.059N     P=0.010 *    P=0.536N     P=0.098N    |P=0.248N     P=0.507      P=0.666      P=0.511N     |
|POLY 1.5           |     P=0.030N*    P=0.009 **   P=0.545N     P=0.059N    |P=0.268N     P=0.445      P=0.619      P=0.504N     |
|POLY 6             |     P=0.088N     P=0.013 *    P=0.512N     P=0.144N    |P=0.211N     P=0.655      P=0.769      P=0.530N     |
|LOGISTIC REGRESSION|     P=0.055N     P=0.014 *    P=0.570N     P=0.105N    |P=1.000N     P=1.000N     P=1.000N     (e)          |
|COCH-ARM / FISHERS |     P=0.011N*    P=0.010 *    P=0.544N     P=0.027N*   |P=0.328N     P=0.375      P=0.600      P=0.500N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 31
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |17/50 (34%)  14/50 (28%)  18/50 (36%)  10/49 (20%)  |
|POLY-3 ADJUSTED (b)|                                                        |37.0%        31.9%        37.8%        28.0%        |
|TERMINAL (d)       |                                                        |13/35 (37%)  13/35 (37%)  17/43 (40%)  8/25 (32%)   |
|FIRST INCIDENCE    |                                                        |625          405          701          343          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.330N     P=0.337N     P=0.388N     P=0.344N     |
|POLY 3             |                                                        |P=0.298N     P=0.390N     P=0.553      P=0.268N     |
|POLY 1.5           |                                                        |P=0.221N     P=0.374N     P=0.533      P=0.192N     |
|POLY 6             |                                                        |P=0.366N     P=0.397N     P=0.578      P=0.345N     |
|LOGISTIC REGRESSION|                                                        |P=0.294N     P=0.388N     P=0.549N     P=0.262N     |
|COCH-ARM / FISHERS |                                                        |P=0.111N     P=0.333N     P=0.500      P=0.098N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Hemorrhage                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |0/50 (0%)    1/50 (2%)    4/50 (8%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|                                                        |0.0%         2.3%         8.4%         2.9%         |
|TERMINAL (d)       |                                                        |0/35 (0%)    0/35 (0%)    3/43 (7%)    0/25 (0%)    |
|FIRST INCIDENCE    |                                                        |---          405          716          343          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.264      P=0.496      P=0.094      P=0.492      |
|POLY 3             |                                                        |P=0.193      P=0.494      P=0.068      P=0.450      |
|POLY 1.5           |                                                        |P=0.237      P=0.495      P=0.065      P=0.466      |
|POLY 6             |                                                        |P=0.161      P=0.496      P=0.072      P=0.438      |
|LOGISTIC REGRESSION|                                                        |P=0.496      P=0.733      P=0.078      P=0.894      |
|COCH-ARM / FISHERS |                                                        |P=0.330      P=0.500      P=0.059      P=0.495      |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 32
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |2/50 (4%)    3/50 (6%)    2/50 (4%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|                                                        |4.4%         6.8%         4.2%         2.9%         |
|TERMINAL (d)       |                                                        |2/35 (6%)    2/35 (6%)    2/43 (5%)    1/25 (4%)    |
|FIRST INCIDENCE    |                                                        |730 (T)      405          730 (T)      730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.402N     P=0.498      P=0.619N     P=0.617N     |
|POLY 3             |                                                        |P=0.403N     P=0.487      P=0.675N     P=0.595N     |
|POLY 1.5           |                                                        |P=0.378N     P=0.489      P=0.682N     P=0.565N     |
|POLY 6             |                                                        |P=0.419N     P=0.491      P=0.664N     P=0.618N     |
|LOGISTIC REGRESSION|                                                        |P=0.343N     P=0.531      P=0.619N     P=0.617N     |
|COCH-ARM / FISHERS |                                                        |P=0.320N     P=0.500      P=0.691N     P=0.508N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Pigmentation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |7/50 (14%)   16/50 (32%)  11/50 (22%)  6/49 (12%)   |
|POLY-3 ADJUSTED (b)|                                                        |15.1%        36.1%        22.8%        17.3%        |
|TERMINAL (d)       |                                                        |5/35 (14%)   12/35 (34%)  9/43 (21%)   2/25 (8%)    |
|FIRST INCIDENCE    |                                                        |362          405          602          641          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.447N     P=0.032 *    P=0.348      P=0.491      |
|POLY 3             |                                                        |P=0.475N     P=0.017 *    P=0.244      P=0.516      |
|POLY 1.5           |                                                        |P=0.385N     P=0.019 *    P=0.232      P=0.584      |
|POLY 6             |                                                        |P=0.527N     P=0.018 *    P=0.266      P=0.469      |
|LOGISTIC REGRESSION|                                                        |P=0.318N     P=0.028 *    P=0.164      P=0.610N     |
|COCH-ARM / FISHERS |                                                        |P=0.216N     P=0.028 *    P=0.218      P=0.516N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 33
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Ovary                                                                                                                            |
|     Thrombosis                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |0/50 (0%)    1/50 (2%)    3/50 (6%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|                                                        |0.0%         2.3%         6.3%         0.0%         |
|TERMINAL (d)       |                                                        |0/35 (0%)    0/35 (0%)    2/43 (5%)    0/25 (0%)    |
|FIRST INCIDENCE    |                                                        |---          405          716          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.575      P=0.496      P=0.162      (e)          |
|POLY 3             |                                                        |P=0.445      P=0.494      P=0.129      (e)          |
|POLY 1.5           |                                                        |P=0.513      P=0.495      P=0.125      (e)          |
|POLY 6             |                                                        |P=0.391      P=0.496      P=0.135      (e)          |
|LOGISTIC REGRESSION|                                                        |P=0.576N     P=0.733      P=0.139      (e)          |
|COCH-ARM / FISHERS |                                                        |P=0.628      P=0.500      P=0.121      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Pancreas                                                                                                                         |
|     Infiltration Cellular Mononuclear Cell                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/49 (2%)    1/50 (2%)    0/50 (0%)    1/50 (2%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    2/48 (4%)    |
|POLY-3 ADJUSTED (b)|     2.2%         2.1%         0.0%         3.2%        |0.0%         0.0%         0.0%         5.6%         |
|TERMINAL (d)       |     1/35 (3%)    1/43 (2%)    0/43 (0%)    1/22 (5%)   |0/35 (0%)    0/35 (0%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      ---          729 (T)     |---          ---          ---          480          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.598      P=0.715N     P=0.459N     P=0.655     |P=0.046 *    (e)          (e)          P=0.229      |
|POLY 3             |     P=0.598N     P=0.748N     P=0.492N     P=0.671     |P=0.038 *    (e)          (e)          P=0.189      |
|POLY 1.5           |     P=0.613N     P=0.751N     P=0.494N     P=0.709     |P=0.039 *    (e)          (e)          P=0.201      |
|POLY 6             |     P=0.589N     P=0.742N     P=0.486N     P=0.636     |P=0.038 *    (e)          (e)          P=0.179      |
|LOGISTIC REGRESSION|     P=0.598      P=0.715N     (e)          P=0.655     |P=0.139      (e)          (e)          P=0.472      |
|COCH-ARM / FISHERS |     P=0.612N     P=0.747N     P=0.495N     P=0.747N    |P=0.043 *    (e)          (e)          P=0.237      |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 34
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Parathyroid Gland                                                                                                                |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/42 (2%)    2/35 (6%)    1/39 (3%)    1/38 (3%)   |0/39 (0%)    0/39 (0%)    0/34 (0%)    0/40 (0%)    |
|POLY-3 ADJUSTED (b)|     2.5%         6.1%         2.8%         3.6%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     1/33 (3%)    2/30 (7%)    1/32 (3%)    0/21 (0%)   |0/29 (0%)    0/28 (0%)    0/30 (0%)    0/19 (0%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      481         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.599      P=0.467      P=0.755      P=0.686     |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.587      P=0.434      P=0.737      P=0.676     |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.591N     P=0.435      P=0.739      P=0.701     |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.556      P=0.435      P=0.738      P=0.655     |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     P=0.502N     P=0.467      P=0.755      P=0.654N    |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.548N     P=0.431      P=0.734      P=0.728     |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis                                                                                                   |
|     Angiectasis                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/48 (0%)    0/49 (0%)    0/49 (0%)    0/46 (0%)   |2/49 (4%)    3/49 (6%)    6/49 (12%)   2/49 (4%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |4.4%         7.0%         12.8%        5.8%         |
|TERMINAL (d)       |     0/35 (0%)    0/42 (0%)    0/42 (0%)    0/22 (0%)   |0/35 (0%)    3/35 (9%)    6/43 (14%)   2/25 (8%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |625          730 (T)      730 (T)      730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.399      P=0.494      P=0.201      P=0.564      |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.351      P=0.475      P=0.147      P=0.591      |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.422      P=0.481      P=0.142      P=0.629      |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.296      P=0.473      P=0.154      P=0.558      |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |P=0.405      P=0.492      P=0.135      P=0.628      |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.558      P=0.500      P=0.134      P=0.691N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 35
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis                                                                                                   |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/48 (2%)    2/49 (4%)    5/49 (10%)   3/46 (7%)   |1/49 (2%)    0/49 (0%)    2/49 (4%)    2/49 (4%)    |
|POLY-3 ADJUSTED (b)|     2.3%         4.3%         10.9%        10.1%       |2.2%         0.0%         4.3%         5.8%         |
|TERMINAL (d)       |     1/35 (3%)    2/42 (5%)    4/42 (10%)   3/22 (14%)  |1/35 (3%)    0/35 (0%)    2/43 (5%)    1/25 (4%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      694          729 (T)     |730 (T)      ---          730 (T)      641          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.065      P=0.564      P=0.149      P=0.156     |P=0.159      P=0.500N     P=0.572      P=0.383      |
|POLY 3             |     P=0.070      P=0.519      P=0.111      P=0.182     |P=0.179      P=0.509N     P=0.519      P=0.414      |
|POLY 1.5           |     P=0.103      P=0.514      P=0.108      P=0.217     |P=0.200      P=0.507N     P=0.511      P=0.443      |
|POLY 6             |     P=0.052      P=0.526      P=0.118      P=0.155     |P=0.165      P=0.508N     P=0.529      P=0.392      |
|LOGISTIC REGRESSION|     P=0.057      P=0.564      P=0.118      P=0.156     |P=0.175      (e)          P=0.572      P=0.415      |
|COCH-ARM / FISHERS |     P=0.196      P=0.508      P=0.107      P=0.292     |P=0.245      P=0.500N     P=0.500      P=0.500      |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Pituitary Gland: Pars Distalis                                                                                                   |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/48 (4%)    2/49 (4%)    0/49 (0%)    0/46 (0%)   |9/49 (18%)   12/49 (24%)  10/49 (20%)  11/49 (22%)  |
|POLY-3 ADJUSTED (b)|     4.5%         4.3%         0.0%         0.0%        |20.0%        27.8%        21.3%        31.9%        |
|TERMINAL (d)       |     2/35 (6%)    2/42 (5%)    0/42 (0%)    0/22 (0%)   |6/35 (17%)   11/35 (31%)  10/43 (23%)  9/25 (36%)   |
|FIRST INCIDENCE    |     729 (T)      729 (T)      ---          ---         |625          568          730 (T)      703          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.116N     P=0.628N     P=0.199N     P=0.345N    |P=0.156      P=0.305      P=0.519N     P=0.138      |
|POLY 3             |     P=0.098N     P=0.674N     P=0.229N     P=0.335N    |P=0.207      P=0.269      P=0.540      P=0.171      |
|POLY 1.5           |     P=0.098N     P=0.679N     P=0.231N     P=0.301N    |P=0.272      P=0.279      P=0.525      P=0.243      |
|POLY 6             |     P=0.098N     P=0.667N     P=0.223N     P=0.365N    |P=0.167      P=0.270      P=0.560      P=0.123      |
|LOGISTIC REGRESSION|     P=0.116N     P=0.628N     (e)          (e)         |P=0.148      P=0.273      P=0.572      P=0.121      |
|COCH-ARM / FISHERS |     P=0.089N     P=0.684N     P=0.242N     P=0.258N    |P=0.430      P=0.312      P=0.500      P=0.401      |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 36
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Preputial Gland                                                                                                                  |
|     Infiltration Cellular Mononuclear Cell                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     20/49 (41%)  25/50 (50%)  27/50 (54%)  26/49 (53%) |                                                    |
|POLY-3 ADJUSTED (b)|     43.1%        52.1%        54.9%        65.4%       |                                                    |
|TERMINAL (d)       |     15/35 (43%)  24/43 (56%)  23/43 (54%)  12/22 (55%) |                                                    |
|FIRST INCIDENCE    |     513          605          429          481         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.002 **   P=0.521      P=0.366      P=0.010 *   |                                                    |
|POLY 3             |     P=0.026 *    P=0.249      P=0.169      P=0.028 *   |                                                    |
|POLY 1.5           |     P=0.047 *    P=0.244      P=0.152      P=0.052     |                                                    |
|POLY 6             |     P=0.017 *    P=0.259      P=0.195      P=0.017 *   |                                                    |
|LOGISTIC REGRESSION|     P=0.102      P=0.279      P=0.128      P=0.119     |                                                    |
|COCH-ARM / FISHERS |     P=0.150      P=0.237      P=0.133      P=0.156     |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Preputial Gland                                                                                                                  |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     13/49 (27%)  6/50 (12%)   7/50 (14%)   3/49 (6%)   |                                                    |
|POLY-3 ADJUSTED (b)|     28.1%        12.6%        14.9%        9.4%        |                                                    |
|TERMINAL (d)       |     9/35 (26%)   6/43 (14%)   7/43 (16%)   1/22 (5%)   |                                                    |
|FIRST INCIDENCE    |     501          729 (T)      729 (T)      481         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.044N*    P=0.027N*    P=0.049N*    P=0.065N    |                                                    |
|POLY 3             |     P=0.032N*    P=0.051N     P=0.096N     P=0.044N*   |                                                    |
|POLY 1.5           |     P=0.021N*    P=0.053N     P=0.098N     P=0.022N*   |                                                    |
|POLY 6             |     P=0.043N*    P=0.049N*    P=0.090N     P=0.077N    |                                                    |
|LOGISTIC REGRESSION|     P=0.015N*    P=0.059N     P=0.095N     P=0.012N*   |                                                    |
|COCH-ARM / FISHERS |     P=0.008N**   P=0.056N     P=0.096N     P=0.006N**  |                                                    |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 37
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Preputial Gland: Duct                                                                                                            |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     18/49 (37%)  20/50 (40%)  18/50 (36%)  16/49 (33%) |                                                    |
|POLY-3 ADJUSTED (b)|     39.2%        41.1%        38.1%        48.1%       |                                                    |
|TERMINAL (d)       |     13/35 (37%)  17/43 (40%)  16/43 (37%)  12/22 (55%) |                                                    |
|FIRST INCIDENCE    |     638          605          655          481         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.153      P=0.475N     P=0.325N     P=0.190     |                                                    |
|POLY 3             |     P=0.303      P=0.510      P=0.540N     P=0.290     |                                                    |
|POLY 1.5           |     P=0.453      P=0.485      P=0.551N     P=0.460     |                                                    |
|POLY 6             |     P=0.208      P=0.542      P=0.515N     P=0.166     |                                                    |
|LOGISTIC REGRESSION|     P=0.262      P=0.482      P=0.513N     P=0.237     |                                                    |
|COCH-ARM / FISHERS |     P=0.314N     P=0.449      P=0.553N     P=0.416N    |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Prostate                                                                                                                         |
|     Infiltration Cellular Mononuclear Cell                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     24/49 (49%)  31/50 (62%)  34/50 (68%)  32/50 (64%) |                                                    |
|POLY-3 ADJUSTED (b)|     52.1%        64.3%        70.2%        75.2%       |                                                    |
|TERMINAL (d)       |     21/35 (60%)  29/43 (67%)  31/43 (72%)  15/22 (68%) |                                                    |
|FIRST INCIDENCE    |     501          625          439          481         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.435      P=0.231      P<0.001 **  |                                                    |
|POLY 3             |     P=0.014 *    P=0.157      P=0.050      P=0.016 *   |                                                    |
|POLY 1.5           |     P=0.026 *    P=0.146      P=0.045 *    P=0.029 *   |                                                    |
|POLY 6             |     P=0.009 **   P=0.179      P=0.064      P=0.010 *   |                                                    |
|LOGISTIC REGRESSION|     P=0.017 *    P=0.190      P=0.045 *    P=0.047 *   |                                                    |
|COCH-ARM / FISHERS |     P=0.098      P=0.135      P=0.043 *    P=0.096     |                                                    |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 38
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Salivary Glands                                                                                                                  |
|     Infiltration Cellular Mononuclear Cell                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     22/49 (45%)  35/50 (70%)  36/50 (72%)  29/50 (58%) |27/48 (56%)  29/50 (58%)  32/50 (64%)  27/49 (55%)  |
|POLY-3 ADJUSTED (b)|     46.2%        71.4%        72.5%        74.5%       |60.3%        65.8%        65.1%        65.1%        |
|TERMINAL (d)       |     16/35 (46%)  31/43 (72%)  31/43 (72%)  18/22 (82%) |22/35 (63%)  25/35 (71%)  28/43 (65%)  16/25 (64%)  |
|FIRST INCIDENCE    |     501          605          429          481         |623          521          533          212          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P<0.001 **   P=0.097      P=0.071      P=0.002 **  |P=0.072      P=0.413      P=0.536N     P=0.104      |
|POLY 3             |     P=0.005 **   P=0.008 **   P=0.006 **   P=0.005 **  |P=0.387      P=0.374      P=0.397      P=0.404      |
|POLY 1.5           |     P=0.026 *    P=0.008 **   P=0.005 **   P=0.021 *   |P=0.449      P=0.414      P=0.352      P=0.481      |
|POLY 6             |     P<0.001 **   P=0.009 **   P=0.007 **   P<0.001 **  |P=0.350      P=0.355      P=0.452      P=0.353      |
|LOGISTIC REGRESSION|     P=0.052      P=0.008 **   P=0.004 **   P=0.038 *   |P=0.259      P=0.341      P=0.348      P=0.422      |
|COCH-ARM / FISHERS |     P=0.232      P=0.010 *    P=0.005 **   P=0.135     |P=0.501N     P=0.512      P=0.282      P=0.536N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Salivary Glands                                                                                                                  |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/49 (2%)    0/50 (0%)    1/50 (2%)    0/50 (0%)   |0/48 (0%)    0/50 (0%)    2/50 (4%)    1/49 (2%)    |
|POLY-3 ADJUSTED (b)|     2.2%         0.0%         2.1%         0.0%        |0.0%         0.0%         4.2%         2.9%         |
|TERMINAL (d)       |     1/35 (3%)    0/43 (0%)    0/43 (0%)    0/22 (0%)   |0/35 (0%)    0/35 (0%)    2/43 (5%)    0/25 (0%)    |
|FIRST INCIDENCE    |     729 (T)      ---          439          ---         |---          ---          730 (T)      703          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.446N     P=0.459N     P=0.738N     P=0.593N    |P=0.173      (e)          P=0.285      P=0.432      |
|POLY 3             |     P=0.446N     P=0.488N     P=0.747N     P=0.571N    |P=0.155      (e)          P=0.256      P=0.450      |
|POLY 1.5           |     P=0.435N     P=0.492N     P=0.752N     P=0.543N    |P=0.185      (e)          P=0.252      P=0.469      |
|POLY 6             |     P=0.477N     P=0.484N     P=0.740N     P=0.595N    |P=0.132      (e)          P=0.260      P=0.435      |
|LOGISTIC REGRESSION|     P=0.203N     (e)          P=0.700N     (e)         |P=0.173      (e)          P=0.285      P=0.449      |
|COCH-ARM / FISHERS |     P=0.402N     P=0.495N     P=0.747N     P=0.495N    |P=0.247      (e)          P=0.258      P=0.505      |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 39
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Seminal Vesicle                                                                                                                  |
|     Infiltration Cellular Mononuclear Cell                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    2/50 (4%)    2/50 (4%)    0/50 (0%)   |                                                    |
|POLY-3 ADJUSTED (b)|     0.0%         4.2%         4.3%         0.0%        |                                                    |
|TERMINAL (d)       |     0/35 (0%)    1/43 (2%)    2/43 (5%)    0/22 (0%)   |                                                    |
|FIRST INCIDENCE    |     ---          644          729 (T)      ---         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.651N     P=0.265      P=0.285      (e)         |                                                    |
|POLY 3             |     P=0.534      P=0.252      P=0.247      (e)         |                                                    |
|POLY 1.5           |     P=0.601N     P=0.248      P=0.244      (e)         |                                                    |
|POLY 6             |     P=0.466      P=0.258      P=0.253      (e)         |                                                    |
|LOGISTIC REGRESSION|     P=0.607N     P=0.211      P=0.285      (e)         |                                                    |
|COCH-ARM / FISHERS |     P=0.495N     P=0.253      P=0.253      (e)         |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin                                                                                                                             |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    2/50 (4%)    3/50 (6%)    0/50 (0%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         4.2%         6.3%         0.0%        |2.2%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/35 (0%)    2/43 (5%)    2/43 (5%)    0/22 (0%)   |0/35 (0%)    0/35 (0%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     ---          729 (T)      439          ---         |607          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.609      P=0.285      P=0.148      (e)         |P=0.345N     P=0.522N     P=0.504N     P=0.583N     |
|POLY 3             |     P=0.437      P=0.250      P=0.130      (e)         |P=0.258N     P=0.511N     P=0.491N     P=0.553N     |
|POLY 1.5           |     P=0.545      P=0.247      P=0.126      (e)         |P=0.278N     P=0.508N     P=0.495N     P=0.534N     |
|POLY 6             |     P=0.358      P=0.256      P=0.136      (e)         |P=0.239N     P=0.512N     P=0.487N     P=0.568N     |
|LOGISTIC REGRESSION|     P=0.492N     P=0.285      P=0.138      (e)         |P=0.246N     P=0.447N     P=0.611N     P=0.433N     |
|COCH-ARM / FISHERS |     P=0.525N     P=0.253      P=0.125      (e)         |P=0.306N     P=0.500N     P=0.500N     P=0.500N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 40
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Epidermis                                                                                                                  |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    2/50 (4%)    2/50 (4%)    0/50 (0%)   |0/50 (0%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         4.2%         4.3%         0.0%        |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/35 (0%)    2/43 (5%)    2/43 (5%)    0/22 (0%)   |0/35 (0%)    0/35 (0%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     ---          729 (T)      729 (T)      ---         |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.642N     P=0.285      P=0.285      (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     P=0.534      P=0.250      P=0.247      (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     P=0.601N     P=0.247      P=0.244      (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     P=0.466      P=0.256      P=0.253      (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          P=0.285      P=0.285      (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     P=0.495N     P=0.253      P=0.253      (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Skin: Epidermis                                                                                                                  |
|     Ulcer                                                                                                                       |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    2/50 (4%)    2/50 (4%)    0/50 (0%)   |1/50 (2%)    0/50 (0%)    0/50 (0%)    0/50 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         4.2%         4.2%         0.0%        |2.2%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     0/35 (0%)    2/43 (5%)    1/43 (2%)    0/22 (0%)   |0/35 (0%)    0/35 (0%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     ---          729 (T)      439          ---         |607          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.604N     P=0.285      P=0.262      (e)         |P=0.345N     P=0.522N     P=0.504N     P=0.583N     |
|POLY 3             |     P=0.534      P=0.250      P=0.251      (e)         |P=0.258N     P=0.511N     P=0.491N     P=0.553N     |
|POLY 1.5           |     P=0.600N     P=0.247      P=0.246      (e)         |P=0.278N     P=0.508N     P=0.495N     P=0.534N     |
|POLY 6             |     P=0.469      P=0.256      P=0.258      (e)         |P=0.239N     P=0.512N     P=0.487N     P=0.568N     |
|LOGISTIC REGRESSION|     P=0.410N     P=0.285      P=0.300      (e)         |P=0.246N     P=0.447N     P=0.611N     P=0.433N     |
|COCH-ARM / FISHERS |     P=0.495N     P=0.253      P=0.253      (e)         |P=0.306N     P=0.500N     P=0.500N     P=0.500N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 41
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hematopoietic Cell Proliferation                                                                                            |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     12/49 (24%)  13/50 (26%)  14/50 (28%)  4/50 (8%)   |18/50 (36%)  22/50 (44%)  15/49 (31%)  10/49 (20%)  |
|POLY-3 ADJUSTED (b)|     25.7%        26.2%        28.1%        12.8%       |39.0%        47.9%        31.1%        28.0%        |
|TERMINAL (d)       |     7/35 (20%)   7/43 (16%)   8/43 (19%)   3/22 (14%)  |14/35 (40%)  16/35 (46%)  12/43 (28%)  5/25 (20%)   |
|FIRST INCIDENCE    |     513          563          429          710         |607          405          589          343          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.201N     P=0.519N     P=0.563      P=0.207N    |P=0.122N     P=0.273      P=0.161N     P=0.299N     |
|POLY 3             |     P=0.197N     P=0.569      P=0.488      P=0.146N    |P=0.088N     P=0.256      P=0.278N     P=0.210N     |
|POLY 1.5           |     P=0.102N     P=0.549      P=0.464      P=0.078N    |P=0.057N     P=0.254      P=0.310N     P=0.144N     |
|POLY 6             |     P=0.307N     P=0.585N     P=0.522      P=0.238N    |P=0.112N     P=0.273      P=0.238N     P=0.272N     |
|LOGISTIC REGRESSION|     P=0.010N*    P=0.387      P=0.363      P=0.106N    |P=0.045N*    P=0.242      P=0.342N     P=0.216N     |
|COCH-ARM / FISHERS |     P=0.020N*    P=0.523      P=0.433      P=0.024N*   |P=0.021N*    P=0.270      P=0.361N     P=0.066N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Spleen                                                                                                                           |
|     Hyperplasia Lymphoid                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/49 (2%)    4/50 (8%)    1/50 (2%)    0/50 (0%)   |1/50 (2%)    3/50 (6%)    1/49 (2%)    0/49 (0%)    |
|POLY-3 ADJUSTED (b)|     2.2%         8.4%         2.1%         0.0%        |2.2%         7.0%         2.1%         0.0%         |
|TERMINAL (d)       |     1/35 (3%)    4/43 (9%)    1/43 (2%)    0/22 (0%)   |0/35 (0%)    3/35 (9%)    1/43 (2%)    0/25 (0%)    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      ---         |645          730 (T)      730 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.249N     P=0.246      P=0.715N     P=0.593N    |P=0.257N     P=0.298      P=0.733N     P=0.583N     |
|POLY 3             |     P=0.251N     P=0.197      P=0.751N     P=0.571N    |P=0.264N     P=0.286      P=0.753N     P=0.555N     |
|POLY 1.5           |     P=0.217N     P=0.192      P=0.754N     P=0.543N    |P=0.245N     P=0.291      P=0.758N     P=0.537N     |
|POLY 6             |     P=0.286N     P=0.204      P=0.745N     P=0.595N    |P=0.276N     P=0.285      P=0.746N     P=0.569N     |
|LOGISTIC REGRESSION|     P=0.249N     P=0.246      P=0.715N     (e)         |P=0.250N     P=0.291      P=0.738      P=0.485N     |
|COCH-ARM / FISHERS |     P=0.159N     P=0.187      P=0.747N     P=0.495N    |P=0.205N     P=0.309      P=0.747      P=0.505N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 42
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach: Epithelium                                                                                                 |
|     Hyperplasia                                                                                                                 |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/49 (4%)    3/50 (6%)    1/50 (2%)    1/50 (2%)   |3/50 (6%)    2/50 (4%)    1/50 (2%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     4.4%         6.3%         2.1%         3.2%        |6.6%         4.7%         2.1%         2.9%         |
|TERMINAL (d)       |     0/35 (0%)    2/43 (5%)    1/43 (2%)    0/22 (0%)   |2/35 (6%)    2/35 (6%)    1/43 (2%)    0/25 (0%)    |
|FIRST INCIDENCE    |     513          644          729 (T)      710         |625          730 (T)      730 (T)      694          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.448N     P=0.551      P=0.465N     P=0.685N    |P=0.270N     P=0.506N     P=0.252N     P=0.433N     |
|POLY 3             |     P=0.363N     P=0.521      P=0.491N     P=0.628N    |P=0.230N     P=0.526N     P=0.290N     P=0.405N     |
|POLY 1.5           |     P=0.337N     P=0.516      P=0.494N     P=0.579N    |P=0.222N     P=0.519N     P=0.296N     P=0.369N     |
|POLY 6             |     P=0.387N     P=0.530      P=0.485N     P=0.669N    |P=0.233N     P=0.526N     P=0.281N     P=0.435N     |
|LOGISTIC REGRESSION|     P=0.247N     P=0.388      P=0.461N     P=0.469N    |P=0.252N     P=0.518N     P=0.309N     P=0.380N     |
|COCH-ARM / FISHERS |     P=0.274N     P=0.510      P=0.492N     P=0.492N    |P=0.199N     P=0.500N     P=0.309N     P=0.309N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Forestomach: Epithelium                                                                                                 |
|     Inflammation Chronic                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/49 (4%)    1/50 (2%)    2/50 (4%)    0/50 (0%)   |1/50 (2%)    2/50 (4%)    2/50 (4%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     4.3%         2.1%         4.3%         0.0%        |2.2%         4.6%         4.2%         2.9%         |
|TERMINAL (d)       |     0/35 (0%)    0/43 (0%)    2/43 (5%)    0/22 (0%)   |0/35 (0%)    1/35 (3%)    1/43 (2%)    0/25 (0%)    |
|FIRST INCIDENCE    |     501          625          729 (T)      ---         |625          722          589          694          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.322N     P=0.486N     P=0.659N     P=0.394N    |P=0.562      P=0.492      P=0.529      P=0.683      |
|POLY 3             |     P=0.298N     P=0.487N     P=0.689N     P=0.335N    |P=0.540      P=0.481      P=0.519      P=0.698      |
|POLY 1.5           |     P=0.261N     P=0.490N     P=0.690N     P=0.294N    |P=0.583      P=0.486      P=0.511      P=0.721      |
|POLY 6             |     P=0.342N     P=0.481N     P=0.683N     P=0.374N    |P=0.506      P=0.481      P=0.529      P=0.679      |
|LOGISTIC REGRESSION|     P=0.061N     P=0.682      P=0.639N     P=0.051N    |P=0.566N     P=0.498      P=0.395      P=0.777      |
|COCH-ARM / FISHERS |     P=0.196N     P=0.492N     P=0.684N     P=0.242N    |P=0.556N     P=0.500      P=0.500      P=0.753N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 43
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Glandular                                                                                                               |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/49 (0%)    1/50 (2%)    0/50 (0%)    2/50 (4%)   |1/50 (2%)    1/50 (2%)    0/50 (0%)    1/50 (2%)    |
|POLY-3 ADJUSTED (b)|     0.0%         2.1%         0.0%         6.3%        |2.2%         2.3%         0.0%         2.8%         |
|TERMINAL (d)       |     0/35 (0%)    1/43 (2%)    0/43 (0%)    1/22 (5%)   |1/35 (3%)    1/35 (3%)    0/43 (0%)    0/25 (0%)    |
|FIRST INCIDENCE    |     ---          729 (T)      ---          481         |730 (T)      730 (T)      ---          343          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.085      P=0.541      (e)          P=0.189     |P=0.651      P=0.762      P=0.459N     P=0.719      |
|POLY 3             |     P=0.108      P=0.512      (e)          P=0.171     |P=0.607N     P=0.750      P=0.490N     P=0.706      |
|POLY 1.5           |     P=0.116      P=0.508      (e)          P=0.194     |P=0.614N     P=0.752      P=0.494N     P=0.726      |
|POLY 6             |     P=0.111      P=0.516      (e)          P=0.152     |P=0.596N     P=0.751      P=0.484N     P=0.688      |
|LOGISTIC REGRESSION|     P=0.177      P=0.541      (e)          P=0.281     |P=0.485N     P=0.762      (e)          P=0.608N     |
|COCH-ARM / FISHERS |     P=0.142      P=0.505      (e)          P=0.253     |P=0.616N     P=0.753N     P=0.500N     P=0.753N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Stomach, Glandular: Glands                                                                                                       |
|     Ectasia                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     17/49 (35%)  10/50 (20%)  20/50 (40%)  5/50 (10%)  |16/50 (32%)  9/50 (18%)   10/50 (20%)  3/50 (6%)    |
|POLY-3 ADJUSTED (b)|     37.8%        21.0%        42.6%        16.1%       |34.3%        20.9%        21.0%        8.3%         |
|TERMINAL (d)       |     16/35 (46%)  10/43 (23%)  19/43 (44%)  5/22 (23%)  |13/35 (37%)  8/35 (23%)   10/43 (23%)  1/25 (4%)    |
|FIRST INCIDENCE    |     712          729 (T)      694          729 (T)     |362          709          730 (T)      480          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.150N     P=0.020N*    P=0.523N     P=0.054N    |P=0.006N**   P=0.085N     P=0.045N*    P=0.010N*    |
|POLY 3             |     P=0.172N     P=0.058N     P=0.399      P=0.037N*   |P=0.005N**   P=0.117N     P=0.111N     P=0.005N**   |
|POLY 1.5           |     P=0.077N     P=0.066N     P=0.379      P=0.014N*   |P=0.003N**   P=0.107N     P=0.118N     P=0.002N**   |
|POLY 6             |     P=0.290N     P=0.049N*    P=0.444      P=0.079N    |P=0.007N**   P=0.118N     P=0.100N     P=0.008N**   |
|LOGISTIC REGRESSION|     P=0.174N     P=0.023N*    P=0.573      P=0.055N    |P=0.003N**   P=0.099N     P=0.119N     P<0.001N**   |
|COCH-ARM / FISHERS |     P=0.013N*    P=0.078N     P=0.368      P=0.003N**  |P<0.001N**   P=0.083N     P=0.127N     P<0.001N**   |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 44
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes                                                                                                                           |
|     Mineralization                                                                                                              |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/49 (4%)    2/50 (4%)    1/50 (2%)    0/50 (0%)   |                                                    |
|POLY-3 ADJUSTED (b)|     4.5%         4.2%         2.1%         0.0%        |                                                    |
|TERMINAL (d)       |     2/35 (6%)    2/43 (5%)    1/43 (2%)    0/22 (0%)   |                                                    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      ---         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.181N     P=0.619N     P=0.428N     P=0.345N    |                                                    |
|POLY 3             |     P=0.173N     P=0.673N     P=0.485N     P=0.328N    |                                                    |
|POLY 1.5           |     P=0.157N     P=0.679N     P=0.490N     P=0.290N    |                                                    |
|POLY 6             |     P=0.192N     P=0.664N     P=0.475N     P=0.364N    |                                                    |
|LOGISTIC REGRESSION|     P=0.181N     P=0.619N     P=0.428N     (e)         |                                                    |
|COCH-ARM / FISHERS |     P=0.122N     P=0.684N     P=0.492N     P=0.242N    |                                                    |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Testes: Germinal Epithelium                                                                                                      |
|     Atrophy                                                                                                                     |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     1/49 (2%)    2/50 (4%)    2/50 (4%)    0/50 (0%)   |                                                    |
|POLY-3 ADJUSTED (b)|     2.2%         4.2%         4.3%         0.0%        |                                                    |
|TERMINAL (d)       |     1/35 (3%)    2/43 (5%)    2/43 (5%)    0/22 (0%)   |                                                    |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      ---         |                                                    |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.418N     P=0.572      P=0.572      P=0.593N    |                                                    |
|POLY 3             |     P=0.431N     P=0.520      P=0.515      P=0.571N    |                                                    |
|POLY 1.5           |     P=0.381N     P=0.515      P=0.510      P=0.543N    |                                                    |
|POLY 6             |     P=0.486N     P=0.528      P=0.525      P=0.595N    |                                                    |
|LOGISTIC REGRESSION|     P=0.418N     P=0.572      P=0.572      (e)         |                                                    |
|COCH-ARM / FISHERS |     P=0.291N     P=0.508      P=0.508      P=0.495N    |                                                    |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 45
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Thymus                                                                                                                           |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     16/40 (40%)  19/48 (40%)  18/46 (39%)  17/49 (35%) |20/47 (43%)  17/43 (40%)  23/46 (50%)  19/48 (40%)  |
|POLY-3 ADJUSTED (b)|     41.0%        40.9%        40.9%        47.0%       |44.6%        42.4%        52.2%        52.5%        |
|TERMINAL (d)       |     11/31 (36%)  17/42 (41%)  15/39 (39%)  9/22 (41%)  |16/34 (47%)  14/32 (44%)  23/41 (56%)  16/25 (64%)  |
|FIRST INCIDENCE    |     501          605          502          481         |362          374          730 (T)      212          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.088      P=0.460N     P=0.482N     P=0.163     |P=0.146      P=0.426N     P=0.523N     P=0.225      |
|POLY 3             |     P=0.337      P=0.585N     P=0.585N     P=0.383     |P=0.207      P=0.506N     P=0.308      P=0.314      |
|POLY 1.5           |     P=0.477      P=0.579N     P=0.578N     P=0.532     |P=0.333      P=0.501N     P=0.304      P=0.459      |
|POLY 6             |     P=0.238      P=0.584      P=0.583N     P=0.260     |P=0.127      P=0.495N     P=0.322      P=0.202      |
|LOGISTIC REGRESSION|     P=0.408N     P=0.566      P=0.554N     P=0.448N    |P=0.348      P=0.458N     P=0.341      P=0.437      |
|COCH-ARM / FISHERS |     P=0.321N     P=0.570N     P=0.555N     P=0.383N    |P=0.484N     P=0.470N     P=0.304      P=0.466N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Thymus                                                                                                                           |
|     Ectopic Parathyroid Gland                                                                                                   |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     3/40 (8%)    1/48 (2%)    3/46 (7%)    1/49 (2%)   |1/47 (2%)    1/43 (2%)    1/46 (2%)    0/48 (0%)    |
|POLY-3 ADJUSTED (b)|     8.1%         2.2%         7.0%         3.3%        |2.3%         2.6%         2.3%         0.0%         |
|TERMINAL (d)       |     2/31 (7%)    1/42 (2%)    3/39 (8%)    1/22 (5%)   |1/34 (3%)    1/32 (3%)    1/41 (2%)    0/25 (0%)    |
|FIRST INCIDENCE    |     694          729 (T)      729 (T)      729 (T)     |730 (T)      730 (T)      730 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.460N     P=0.220N     P=0.560N     P=0.452N    |P=0.357N     P=0.748      P=0.720N     P=0.561N     |
|POLY 3             |     P=0.390N     P=0.235N     P=0.596N     P=0.380N    |P=0.350N     P=0.733      P=0.755N     P=0.548N     |
|POLY 1.5           |     P=0.343N     P=0.237N     P=0.597N     P=0.321N    |P=0.335N     P=0.734      P=0.759N     P=0.529N     |
|POLY 6             |     P=0.434N     P=0.232N     P=0.591N     P=0.439N    |P=0.360N     P=0.734      P=0.749N     P=0.563N     |
|LOGISTIC REGRESSION|     P=0.461N     P=0.231N     P=0.588N     P=0.441N    |P=0.357N     P=0.748      P=0.720N     (e)          |
|COCH-ARM / FISHERS |     P=0.255N     P=0.243N     P=0.593N     P=0.236N    |P=0.303N     P=0.730      P=0.747      P=0.495N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 46
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Thymus                                                                                                                           |
|     Hyperplasia Lymphoid                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     0/40 (0%)    0/48 (0%)    0/46 (0%)    0/49 (0%)   |0/47 (0%)    0/43 (0%)    2/46 (4%)    0/48 (0%)    |
|POLY-3 ADJUSTED (b)|     0.0%         0.0%         0.0%         0.0%        |0.0%         0.0%         4.5%         0.0%         |
|TERMINAL (d)       |     0/31 (0%)    0/42 (0%)    0/39 (0%)    0/22 (0%)   |0/34 (0%)    0/32 (0%)    2/41 (5%)    0/25 (0%)    |
|FIRST INCIDENCE    |     ---          ---          ---          ---         |---          ---          730 (T)      ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |P=0.550      (e)          P=0.280      (e)          |
|POLY 3             |     (e)          (e)          (e)          (e)         |P=0.440      (e)          P=0.242      (e)          |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |P=0.503      (e)          P=0.238      (e)          |
|POLY 6             |     (e)          (e)          (e)          (e)         |P=0.384      (e)          P=0.249      (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          P=0.280      (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |P=0.604      (e)          P=0.242      (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Thyroid Gland: Follicle                                                                                                          |
|     Cyst                                                                                                                        |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     2/49 (4%)    2/50 (4%)    2/50 (4%)    0/50 (0%)   |5/49 (10%)   3/50 (6%)    3/50 (6%)    4/50 (8%)    |
|POLY-3 ADJUSTED (b)|     4.5%         4.2%         4.3%         0.0%        |11.3%        7.0%         6.3%         11.5%        |
|TERMINAL (d)       |     2/35 (6%)    2/43 (5%)    2/43 (5%)    0/22 (0%)   |5/35 (14%)   2/35 (6%)    3/43 (7%)    4/25 (16%)   |
|FIRST INCIDENCE    |     729 (T)      729 (T)      729 (T)      ---         |730 (T)      709          730 (T)      730 (T)      |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.249N     P=0.619N     P=0.619N     P=0.345N    |P=0.500      P=0.353N     P=0.249N     P=0.572      |
|POLY 3             |     P=0.258N     P=0.673N     P=0.679N     P=0.328N    |P=0.553N     P=0.373N     P=0.320N     P=0.624      |
|POLY 1.5           |     P=0.222N     P=0.679N     P=0.683N     P=0.290N    |P=0.530N     P=0.367N     P=0.330N     P=0.593N     |
|POLY 6             |     P=0.298N     P=0.664N     P=0.668N     P=0.364N    |P=0.543      P=0.371N     P=0.306N     P=0.577      |
|LOGISTIC REGRESSION|     P=0.249N     P=0.619N     P=0.619N     (e)         |P=0.488      P=0.356N     P=0.249N     P=0.572      |
|COCH-ARM / FISHERS |     P=0.159N     P=0.684N     P=0.684N     P=0.242N    |P=0.472N     P=0.346N     P=0.346N     P=0.487N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 47
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Tooth                                                                                                                            |
|     Malformation                                                                                                                |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     6/6 (100%)   0/0 (0%)     1/1 (100%)   2/2 (100%)  |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     |
|POLY-3 ADJUSTED (b)|     100.0%       0.0%         100.0%       100.0%      |0.0%         0.0%         0.0%         0.0%         |
|TERMINAL (d)       |     4/4 (100%)   0/0 (0%)     1/1 (100%)   2/2 (100%)  |0/0 (0%)     0/0 (0%)     0/0 (0%)     0/0 (0%)     |
|FIRST INCIDENCE    |     663          ---          729 (T)      729 (T)     |---          ---          ---          ---          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 3             |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 1.5           |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|POLY 6             |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|LOGISTIC REGRESSION|     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|COCH-ARM / FISHERS |     (e)          (e)          (e)          (e)         |(e)          (e)          (e)          (e)          |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Urinary Bladder                                                                                                                  |
|     Infiltration Cellular Mononuclear Cell                                                                                      |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |     12/49 (24%)  17/50 (34%)  9/50 (18%)   10/50 (20%) |28/50 (56%)  31/50 (62%)  29/50 (58%)  22/50 (44%)  |
|POLY-3 ADJUSTED (b)|     26.2%        35.2%        18.4%        29.8%       |60.0%        66.8%        60.4%        55.1%        |
|TERMINAL (d)       |     9/35 (26%)   15/43 (35%)  6/43 (14%)   6/22 (27%)  |24/35 (69%)  23/35 (66%)  28/43 (65%)  12/25 (48%)  |
|FIRST INCIDENCE    |     583          625          429          481         |362          374          589          480          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |     P=0.478      P=0.384      P=0.194N     P=0.351     |P=0.533N     P=0.338      P=0.230N     P=0.474      |
|POLY 3             |     P=0.423N     P=0.235      P=0.254N     P=0.463     |P=0.283N     P=0.318      P=0.567      P=0.403N     |
|POLY 1.5           |     P=0.336N     P=0.223      P=0.271N     P=0.590     |P=0.206N     P=0.309      P=0.536      P=0.314N     |
|POLY 6             |     P=0.477N     P=0.255      P=0.230N     P=0.353     |P=0.330N     P=0.365      P=0.557N     P=0.452N     |
|LOGISTIC REGRESSION|     P=0.232N     P=0.225      P=0.296N     P=0.548     |P=0.252N     P=0.281      P=0.549N     P=0.392N     |
|COCH-ARM / FISHERS |     P=0.172N     P=0.207      P=0.294N     P=0.384N    |P=0.082N     P=0.342      P=0.500      P=0.159N     |
|=================================================================================================================================|
       Date:  10/25/99                           EXPERIMENT: 88050 TEST: 06                                            Page 48
                     Statistical Analysis of Non-neoplastic Lesions in       Mice(B6C3F1)  -                 METHACRYLONITRILE
                                         Terminal Sacrifice at 105 weeks 
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus                                                                                                                           |
|     Hydrometra                                                                                                                  |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |23/50 (46%)  28/50 (56%)  31/50 (62%)  20/50 (40%)  |
|POLY-3 ADJUSTED (b)|                                                        |49.6%        60.7%        62.4%        49.0%        |
|TERMINAL (d)       |                                                        |18/35 (51%)  21/35 (60%)  26/43 (61%)  10/25 (40%)  |
|FIRST INCIDENCE    |                                                        |607          405          533          480          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.325      P=0.219      P=0.344      P=0.337      |
|POLY 3             |                                                        |P=0.483N     P=0.188      P=0.141      P=0.564N     |
|POLY 1.5           |                                                        |P=0.405N     P=0.189      P=0.114      P=0.494N     |
|POLY 6             |                                                        |P=0.526N     P=0.202      P=0.181      P=0.569      |
|LOGISTIC REGRESSION|                                                        |P=0.381N     P=0.166      P=0.095      P=0.492N     |
|COCH-ARM / FISHERS |                                                        |P=0.237N     P=0.212      P=0.080      P=0.343N     |
|=================================================================================================================================|
|                   |                                                        |                                                    |
|                   |                              Males                     |                       Females                      |
|Dose               |     0 MG/KG      1.5          3 MG/KG      6 MG/KG     |0 MG/KG      1.5          3 MG/KG      6 MG/KG      |
|                   |                  MG/KG                                 |             MG/KG                                  |
|=================================================================================================================================|
|                                                                                                                                 |
|Uterus: Endometrium                                                                                                              |
|     Hyperplasia Cystic                                                                                                          |
|                                                                                                                                 |
|                                                                                                                                 |
|---------------------------------------------------------------------------------------------------------------------------------|
|LESION RATES       |                                                        |                                                    |
|-----------        |                                                        |                                                    |
|OVERALL (a)        |                                                        |27/50 (54%)  24/50 (48%)  24/50 (48%)  32/50 (64%)  |
|POLY-3 ADJUSTED (b)|                                                        |57.7%        54.4%        50.0%        74.0%        |
|TERMINAL (d)       |                                                        |20/35 (57%)  20/35 (57%)  23/43 (54%)  18/25 (72%)  |
|FIRST INCIDENCE    |                                                        |593          405          589          343          |
|-------------------|                                                        |                                                    |
|STATISTICAL TESTS  |                                                        |                                                    |
|-------------------|                                                        |                                                    |
|LIFE TABLE         |                                                        |P=0.007 **   P=0.365N     P=0.099N     P=0.017 *    |
|POLY 3             |                                                        |P=0.063      P=0.458N     P=0.291N     P=0.072      |
|POLY 1.5           |                                                        |P=0.079      P=0.421N     P=0.309N     P=0.105      |
|POLY 6             |                                                        |P=0.053      P=0.482N     P=0.273N     P=0.054      |
|LOGISTIC REGRESSION|                                                        |P=0.039 *    P=0.440N     P=0.250N     P=0.092      |
|COCH-ARM / FISHERS |                                                        |P=0.130      P=0.345N     P=0.345N     P=0.208      |
|=================================================================================================================================|
(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).